Gamma secretase modulators

ABSTRACT

This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (Chemical formula should be inserted here as it appears on abstract in paper form). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer&#39;s Disease using the compounds of formula (I).

REFERENCE TO RELATED APPLICATION

This Application claims the benefit of U.S. Provisional Application No.61/139,665 filed Dec. 22, 2008.

FIELD OF THE INVENTION

The present invention relates to certain heterocyclic compounds usefulas gamma secretase modulators (including inhibitors, antagonists and thelike), pharmaceutical compositions comprising the compounds, and methodsof treating various diseases using the compounds and compositions.Examples of the diseases and conditions include, for example, Alzheimersdisease, mild cognitive impairment (MCI), Downs Syndrome, Glaucoma,Cerebral amyloid angiopathy, stroke or dementia, Microgliosis and braininflammation, and Olfactory function loss.

BACKGROUND OF THE INVENTION

Alzheimer's disease is a disease characterized by degeneration and lossof neurons and also by the formation of senile plaques andneurofibrillary change. Presently, treatment of Alzheimer's disease islimited to symptomatic therapies with a symptom-improving agentrepresented by an acetylcholinesterase inhibitor, and the basic remedywhich prevents progress of the disease has not been developed. A methodof controlling the cause of onset of pathologic conditions needs to bedeveloped for creation of the basic remedy of Alzheimer's disease.

Aβ protein, which is a metabolite of amyloid precursor protein(hereinafter referred to as APP), is considered to be greatly involvedin degeneration and loss of neurons as well as onset of dementialconditions (for example, see Klein W L, et al Proceeding NationalAcademy of Science USA, Sep. 2, 2003, 100(18), p. 10417-22, suggest amolecular basis for reversible memory loss.

Nitsch R M, and 16 others, Antibodies against β-amyloid slow cognitivedecline in Alzheimer's disease, Neuron, May 22, 2003, 38(4), p. 547-554)suggest that the main components of Aβ protein are Aβ40 consisting of 40amino acids and Aβ42 having two additional amino acids at theC-terminal. The Aβ40 and Aβ42 tend to aggregate (for example, seeJarrell J T et al, The carboxy terminus of the β amyloid protein iscritical for the seeding of amyloid formation: implications for thepathogenesis of Alzheimer's disease, Biochemistry, May 11, 1993, 32(18),p. 4693-4697) and constitute the main components of senile plaques (forexample, (Glenner G G, et al, Alzheimer's disease: initial report of thepurification and characterization of a novel cerebrovascular amyloidprotein, Biochemical and Biophysical Research Communications, May 16,1984, 120(3), p. 885-90. See also Masters C L, et al, Amyloid plaquecore protein in Alzheimer disease and Down syndrome, Proceeding NationalAcademy of Science USA, June 1985, 82(12), p. 4245-4249.).

Furthermore, it is known that mutations of APP and presenelin genes,which is are observed in familial Alzheimer's disease, increaseproduction of Aβ40 and Aβ42 (for example, see Gouras G K, et al,Intraneuronal Aβ142 accumulation in human brain, American Journal ofPathology, January 2000, 156(1), p. 15-20. Also, see Scheuner D, et al,Nature Medicine, August 1996, 2(8), p. 864-870; and Forman M S, et al,Differential effects of the Swedish mutant amyloid precursor protein onβ-amyloid accumulation and secretion in neurons and normeuronal cells,Journal of Biological Chemistry, Dec. 19, 1997, 272(51), p.32247-32253.). Therefore, compounds which reduce production of Aβ40 andAβ42 are expected to be agents for controlling progress of Alzheimer'sdisease or for preventing the disease.

These Aβs are produced when APP is cleaved by beta secretase andsubsequently cleaved by gamma secretase. In consideration of this,creation of inhibitors of γ-secretase and β-secretase has been attemptedfor the purpose of reducing production of Aβs. Many of these knownsecretase inhibitors are peptides or peptidomimetics such as L-685,458.L-685,458, an aspartyl protease transition state mimic, is a potentinhibitor of γ-secretase activity, Biochemistry, Aug. 1, 2000, 39(30),p. 8698-8704).

Also of interest in connection with the present invention are: US2007/0117798 (Eisai, published May 24, 2007); US 2007/0117839 (Eisai,published May 24, 2007); US 2006/0004013 (Eisai, published Jan. 5,2006); WO 2005/110422 (Boehringer Ingelheim, published Nov. 24, 2005);WO 2006/045554 (Cellzone AG, published May 4, 2006); WO 2004/110350(Neurogenetics, published Dec. 23, 2004); WO 2004/071431 (MyriadGenetics, published Aug. 26, 2004); US 2005/0042284 (Myriad Genetics,published Feb. 23, 2005) and WO 2006/001877 (Myriad Genetics, publishedJan. 5, 2006).

There is a need for new compounds, formulations, treatments andtherapies to treat diseases and disorders associated with Aβ. It is,therefore, an object of this invention to provide compounds useful inthe treatment or prevention or amelioration of such diseases anddisorders.

SUMMARY OF THE INVENTION

In its many embodiments, the present invention provides a novel class ofcompounds as gamma secretase modulators (including inhibitors,antagonists and the like), methods of preparing such compounds,pharmaceutical compositions comprising one or more such compounds,methods of preparing pharmaceutical formulations comprising one or moresuch compounds, and methods of treatment, prevention, inhibition oramelioration of one or more diseases associated with the Aβ using suchcompounds or pharmaceutical compositions.

This invention provides novel compounds that are gamma secretasemodulators, of the formula:

or a pharmaceutically acceptable salt, ester, or solvate thereof,wherein all substituents are defined below, and all substituents areindependently selected.

This invention also provides compounds of formula (I).

This invention also includes the compounds of formula I in all itsisolated forms.

This invention also provides compounds of formula (I) in pure andisolated form.

This invention also provides compounds of formula (I) selected from thegroup consisting of: compounds 2A, 3A, 4A, 5A, 6A, 7A, 8A, 2B, 3B, 4B,5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D, 6D, 7D, 8D,2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I, 3I,4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M, 4M, 5M,2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, 5P and compounds 9, and 15to 26.

This invention also provides compounds of formula (I) selected from thegroup consisting of: compounds 2A, 3A, 4A, 5A, 6A, 7A, 8A, 2B, 3B, 4B,5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D, 6D, 7D, 8D,2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I, 3I,4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M, 4M, 5M,2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, and 5P.

This invention also provides compounds of formula (I) selected from thegroup consisting of compounds 9, and 15 to 26.

This invention also provides pharmaceutical compositions comprising aneffective amount of one or more (e.g., one) compounds of formula (I), ora pharmaceutically acceptable salt, ester or solvate thereof, and apharmaceutically acceptable carrier.

This invention also provides pharmaceutical compositions comprising aneffective amount of one or more (e.g., one) compounds of formula (I), ora pharmaceutically acceptable salt, ester or solvate thereof, and aneffective amount of one or more (e.g., one) other pharmaceuticallyactive ingredients (e.g., drugs), and a pharmaceutically acceptablecarrier.

The compounds of Formula (I) can be useful as gamma secretase modulatorsand can be useful in the treatment and prevention of diseases such as,for example, central nervous system disorders such as Alzheimers diseaseand Downs Syndrome.

Thus, this invention also provides methods for: (1) method formodulating (including inhibiting, antagonizing and the like)gamma-secretase; (2) treating one or more neurodegenerative diseases;(3) inhibiting the deposition of amyloid protein (e.g., amyloid betaprotein) in, on or around neurological tissue (e.g., the brain); (4)Alzheimer's disease; and (5) treating Downs syndrome; wherein eachmethod comprises administering an effective amount of one or more (e.g.,one) compounds of formula (I) to a patient in need of such treatment.

This invention also provides combination therapies for (1) modulatinggamma-secretase, or (2) treating one or more neurodegenerative diseases,or (3) inhibiting the deposition of amyloid protein (e.g., amyloid betaprotein) in, on or around neurological tissue (e.g., the brain), or (4)treating Alzheimer's disease. The combination therapies are directed tomethods comprising the administration of an effective amount of one ormore (e.g. one) compounds of formula (I) and the administration of aneffective amount of one or more (e.g., one) other pharmaceutical activeingredients (e.g., drugs).

This invention also provides methods for: (1) treating mild cognitiveimpairment; (2) treating glaucoma; (3) treating cerebral amyloidangiopathy; (4) treating stroke; (5) treating dementia; (6) treatingmicrogliosis; (7) treating brain inflammation; and (8) treatingolfactory function loss; wherein each method comprises administering aneffective amount of one or more (e.g., one) compounds of formula (I) toa patient in need of such treatment.

This invention also provides a kit comprising, in separate containers,in a single package, pharmaceutical compositions for use in combination,wherein one container comprises an effective amount of a compound offormula (I) in a pharmaceutically acceptable carrier, and anothercontainer (i.e., a second container) comprises an effective amount ofanother pharmaceutically active ingredient (as described below), thecombined quantities of the compound of formula (I) and the otherpharmaceutically active ingredient being effective to treat the diseasesor conditions mentioned in any of the above methods.

This invention also provides any of the above mentioned methods,pharmaceutical compositions or kit wherein the compound of formula (I)is selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, 8D, 2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H,5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M,3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, and 5P

This invention also provides any of the above mentioned methods,pharmaceutical compositions or kit wherein the compound of formula (I)is selected from the group consisting of: compounds 9, and 15 to 26.

DETAILED DESCRIPTION OF THE INVENTION

This invention provides compounds, useful as gamma secretase modulators,of formula (I):

or a pharmaceutically acceptable salt, ester, or solvate thereof,wherein:

G, U, R⁶, R⁷, R⁹, and R¹⁰, are independently selected; letters (A) and(B) in formula (I) are reference letters to identify the rings presentin formula (I);

G is selected from the group consisting of: N(R¹⁴), C(O), O and S;

U is CR⁵ or N;

the dotted line in Ring (B) represents an optional bond;

Ring (B) is a 5 to 8 membered ring (including the atoms common to Ring(A)), and: (1) when U is CR⁵ said Ring (B) optionally comprising 1 to 2heteroatoms independently selected from the group consisting of O, NR²and S, and (2) when U is N said Ring (B) optionally comprises 1 to 2additional heteroatoms independently selected from the group consistingof O, NR² and S; and said Ring (B) is optionally substituted with 1 to 5independently selected R²¹ groups;

Each R² is independently selected from the group consisting of: H, —OH,—O-alkyl (i.e., alkoxy), —O-(halo substituted alky) (such as, forexample, —O-fluoroalkyl), —NH(R⁴), —N(R⁴)₂ (wherein each R⁴ isindependently selected), —NH₂, —S(O)R⁴, —S(O)(OR⁴), —S(O)₂R⁴,—S(O)₂(OR⁴), —S(O)NHR⁴, —S(O)N(R⁴)₂, —S(O)NH₂, —S(O)₂NHR⁴, —S(O)₂N(R⁴)₂,—S(O)₂NH₂, —CN, —C(O)₂R⁴, —C(O)NHR⁴, —C(O)N(R⁴)₂, —C(O)NH₂, —C(O)R⁴,unsubstituted aryl, substituted aryl, unsubstituted heteroaryl,substituted heteroaryl, unsubstituted alkyl, substituted alkyl,unsubstituted arylalkyl-, substituted arylalkyl-, unsubstitutedheteroarylalkyl-, substituted heteroarylalkyl-, unsubstituted alkenyl,substituted alkenyl, unsubstituted alkynyl, substituted alkynyl,unsubstituted cycloalkyl, and substituted cycloalkyl, wherein saidsubstituted aryl, heteroaryl, alkyl, arylalkyl-, heteroarylalkyl-,alkenyl, alkynyl and cycloalkyl groups are substituted with 1 to 5independently selected R²¹ groups;

each R⁴ is independently selected from the group consisting of:unsubstituted aryl, substituted aryl, unsubstituted heteroaryl,substituted heteroaryl, unsubstituted alkyl, substituted alkyl,unsubstituted arylalkyl-, substituted arylalkyl-, unsubstitutedheteroarylalkyl-, substituted heteroarylalkyl-, unsubstituted alkenyl,substituted alkenyl, unsubstituted alkynyl, substituted alkynyl,unsubstituted cycloalkyl, and substituted cycloalkyl, wherein saidsubstituted aryl, heteroaryl, alkyl, arylalkyl-, heteroarylalkyl-,alkenyl, alkynyl and cycloalkyl groups are substituted with 1 to 5independently selected R²¹ groups;

R⁵ is selected from the group consisting of: H, alkyl-, alkenyl- andalkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-,heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-; andwherein each of said R⁵ alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-,alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-,heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-groups areoptionally substituted with 1-5 independently selected R²¹ substituents;

R⁶ and R⁷ are each independently selected from the group consisting of:H, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, alkyl-,alkenyl- and alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-,cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl- andheterocyclyalkyl-, benzofusedcycloalkyl (i.e., fused benzocycloalkyl),fused benzoheterocycloalkyl, fused heteroarylcycloalkyl, fusedheteroarylheterocycloalkyl; and wherein each of said R⁶ and R⁷ alkyl-,alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-,cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl-,heterocyclyalkyl-, benzofusedcycloalkyl, fused benzoheterocycloalkyl,fused heteroarylcycloalkyl, and fused heteroarylheterocycloalkyl groupis optionally substituted with 1-5 independently selected R²¹substituents; or

R⁶ and R⁷, taken together with the carbon atom to which they are bound,form a spirocyclic carbocyclic moiety or a spirocyclic heterocyclicmoiety, and:

-   -   (a) optionally, said spirocyclic carbocyclic moiety is        substituted with 1-4 independently selected R²¹ substituents,    -   (b) optionally, said spirocyclic heterocyclic moiety is        substituted with 1-4 independently selected R²¹ substituents,    -   (c) optionally, said spirocyclic carbocyclic moiety is fused        with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl ring        to form a fused ring moiety, and optionally, each ring of said        fused ring moiety is substituted with 1-4 independently selected        R²¹ substituents;    -   (d) optionally, said spirocyclic heterocyclic moiety is fused        with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl ring        to form a fused ring moiety, and optionally, each ring of said        fused ring moiety is substituted with 1-4 independently selected        R²¹ substituents;

R⁹ is selected from the group consisting of: alkyl-, alkenyl-, alkynyl-,aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-,heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, and,optionally, each R⁹ group is substituted with 1-3 independently selectedR²¹ groups;

R¹⁰ is selected from the group consisting of a bond, alkyl-, alkenyl-,alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-,heteroaryl-, heteroarylalkyl-, heterocyclyl-, heterocyclyalkyl-,

wherein X is selected from the group consisting of: O, N(R¹⁴) or S; and,optionally, each of said R¹⁰ groups are substituted with 1-3independently selected R²¹ substitutents;

R⁹ is selected from the group consisting of alkyl-, alkenyl- andalkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-,heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-,wherein each of said alkyl-, alkenyl- and alkynyl-, aryl-, arylalkyl-,alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-,heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl- can beunsubstituted or optionally independently substituted with 1-3substituents which can be the same or different, each substituent beingindependently selected from the group consisting of the moieties shownbelow,

R¹⁴ is selected from the group consisting of H, alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl,heterocyclylalkyl, heterocyclyalkenyl-, aryl, arylalkyl, heteroaryl,heteroarylalkyl, —CN, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶),—S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), C(═NOR¹⁵)R¹⁶, and—P(O)(OR¹⁵)(OR¹⁶), and wherein each of the alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl,heterocyclylalkyl, heterocyclyalkenyl-, aryl, arylalkyl, heteroaryl, andheteroarylalkyl groups in are independently unsubstituted or substitutedby 1 to 5 R²¹ group;

Each R^(15A) is independently selected from the group consisting ofalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,arylcycloalkyl, arylheterocyclyl, (R¹⁸)₁₋₅-alkyl, (R¹⁸)₁₋₅-cycloalkyl,(R¹⁸)₁₋₅-cycloalkylalkyl, (R¹⁸)₁₋₅-heterocyclyl,(R¹⁸)₁₋₅-heterocyclylalkyl, (R¹⁸)₁₋₅-aryl, (R¹⁸)₁₋₅-arylalkyl,(R¹⁸)₁₋₅-heteroaryl and (R¹⁸)₁₋₅-heteroarylalkyl; and wherein each R¹⁸in each group can be on any substitutable atom;

Each R^(16A) is independently selected from the group consisting ofalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,arylcycloalkyl, arylheterocyclyl, (R¹⁸)₁₋₅-alkyl, (R¹⁸)₁₋₅-cycloalkyl,(R¹⁸)₁₋₅-cycloalkylalkyl, (R¹⁸)₁₋₅-heterocyclyl,(R¹⁸)₁₋₅-heterocyclylalkyl, (R¹⁸)₁₋₅-aryl, (R¹⁸)₁₋₅-arylalkyl,(R¹⁸)₁₋₅-heteroaryl and (R¹⁸)₁₋₅-heteroarylalkyl; and wherein each R¹⁸in each group can be on any substitutable atom;

R¹⁵, R¹⁶ and R¹⁷ are independently selected from the group consisting ofH, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,arylcycloalkyl, arylheterocyclyl, (R¹⁸)₁₋₅-alkyl, (R¹⁸)₁₋₅-cycloalkyl,(R¹⁸)₁₋₅-cycloalkylalkyl, (R¹⁸)₁₋₅-heterocyclyl,(R¹⁸)₁₋₅-heterocyclylalkyl, (R¹⁸)₁₋₅-aryl, (R¹⁸)₁₋₅-arylalkyl,(R¹⁸)₁₋₅-heteroaryl and

(R¹⁸)₁₋₅-heteroarylalkyl; and wherein each R¹⁸ in each group can be onany substitutable atom;

Each R¹⁸ is independently selected from the group consisting of alkyl,alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NO₂, halo,heteroaryl, HO-alkyoxyalkyl, —CF₃, —CN, alkyl-CN, —C(O)R¹⁹, —C(O)OH,—C(O)OR¹⁹, —C(O)NHR²⁰, —C(O)NH₂, —C(O)NH₂—C(O)N(alkyl)₂,—C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR¹⁹, —S(O)₂R²⁰,—S(O)NH₂, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl),—S(O)₂NH₂, —S(O)₂NHR¹⁹, —S(O)₂NH(heterocyclyl), —S(O)₂N(alkyl)₂,—S(O)₂N(alkyl)(aryl), —OCF₃, —OH, —OR²⁰, —O-heterocyclyl,—O-cycloalkylalkyl, —O-heterocyclylalkyl, —NH₂, —NHR²⁰, —N(alkyl)₂,—N(arylalkyl)₂, —N(arylalkyl)-(heteroarylalkyl), —NHC(O)R²⁰, —NHC(O)NH₂,—NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl),—N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)₂R²⁰, —NHS(O)₂NH(alkyl),—NHS(O)₂N(alkyl)(alkyl), —N(alkyl)S(O)₂NH(alkyl) and—N(alkyl)S(O)₂N(alkyl)(alkyl);

or, two R¹⁸ moieties on adjacent carbons can be taken together with theatoms to which they are bound to form:

R¹⁹ is selected from the group consisting of: alkyl, cycloalkyl, aryl,arylalkyl and heteroarylalkyl;

R²⁹ is selected from the group consisting of: alkyl, cycloalkyl, aryl,halo substituted aryl, arylalkyl, heteroaryl and heteroarylalkyl;

Each R²¹ is independently selected from the group consisting of alkyl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, halo, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵,—C(O)N(R¹⁵)(R¹⁶), —SF₅, —OSF₅, —Si(R^(15A))₃ wherein each R^(15A) isindependently selected, —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —CH(R¹⁵)(R¹⁶),—S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶),-alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶,—CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶),—N(R¹⁵)S(O)R^(16A), —N(R¹⁵)S(O)₂R^(16A), —CH₂—N(R¹⁵)S(O)₂R^(16A),—N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷),—CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶,—S(O)R^(16A), —N₃, —NO₂ and —S(O)₂R^(15A); and, optionally, each of saidalkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl,heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,alkenyl and alkynyl R²¹ groups are substituted with 1 to 5 independentlyselected R²² groups; and

Each R²² is independently selected from the group consisting of: alkyl,cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, halo,—CF₃, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵, -alkyl-C(O)OR¹⁵,C(O)N(R¹⁵)(R¹⁶),), —SF₅, —OSF₅, —Si(R^(15A))₃ wherein each R^(15A) isindependently selected, —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶),—C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶),—N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶, —N(R¹⁵)S(O)R^(16A),—N(R¹⁵)S(O)₂R^(16A), —CH₂—N(R¹⁵)S(O)₂R^(16A), —N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷),—N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷),—CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —N₃,═NOR¹⁵, —NO₂, —S(O)R^(15A) and —S(O)₂R^(15A).

Those skilled in the art will appreciate that the moiety:

can have the stereochemistry

The moiety

can have the stereochemistry

Thus, in one embodiment of this invention the R⁶ and R⁷ moieties canhave the stereochemistry:

And in another embodiment of this invention the R⁶ and R⁷ moieties canhave the stereochemistry:

The R⁶ and R⁷ benzofusedcycloalkyl (i.e., fused benzocycloalkyl), fusedbenzoheterocycloalkyl, fused heteroarylcycloalkyl, and fusedheteroarylheterocycloalkyl groups, can be optionally substituted with1-5 independently selected R²¹ groups. In one example, the R²¹ groupsare halo (e.g., F).

Examples of the fused ring R⁶ and R⁷ groups include, but are not limitedto:

wherein each Y is independently selected from the group consisting of:—O—, —NR¹⁴— and —C(R²¹)_(q)— (wherein q is 0, 1 or 2 and each R²¹ isindependently selected), and wherein R¹⁴ and R²¹ are as defined forformula (I). Examples of these fused ring R⁶ and R⁷ groups include, forexample:

The compounds of this invention are useful for treating central nervoussystem disorders such as, for example, neurodegenerative diseases suchas Alzheimer's disease and other diseases relating to the deposition ofamyloid protein. They are especially useful for reducing Amyloid beta(hereinafter referred to as Aβ) production which is effective in thetreatment of diseases caused by Aβ such as, for example, Alzheimers andDown Syndrome.

Thus, for example, the compounds of this invention can be used to treatthe following diseases or conditions: Alzheimers disease, mild cognitiveimpairment (MCI), Downs Syndrome, Glaucoma (Guo et. al., Proc. Natl.Acad. Sci. USA 104, 13444-13449 (2007)), Cerebral amyloid angiopathy,stroke or dementia (Frangione et al., Amyloid: J. Protein foldingDisord. 8, suppl. 1, 36-42 (2001), Microgliosis and brain inflammation(M P Lamber, Proc. Natl. Acad. Sci. USA 95, 6448-53 (1998)), andOlfactory function loss (Getchell, et. al. Neurobiology of Aging,663-673, 24, 2003).

In one embodiment R¹⁰ is selected from the group consisting of a bond,alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-,cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-, heterocyclyl-,heterocyclyalkyl-,

wherein X is selected from the group consisting of: O, N(R¹⁴) or S; and,optionally, each of said R¹⁰ groups are substituted with 1-3independently selected R²¹ substitutents.

In one embodiment of this invention U is CR⁵.

In another embodiment of this invention U is N.

In one embodiment of this invention B is a five membered ring.

In another embodiment of this invention B is a five membered ring andthe optional bond is present.

In another embodiment of this invention B is a five membered ring andthe optional bond is absent.

In one embodiment of this invention B is a six membered ring.

In another embodiment of this invention B is a six membered ring and theoptional bond is present.

In another embodiment of this invention B is a six membered ring and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring.

In another embodiment of this invention B is a seven membered ring andthe optional bond is present.

In another embodiment of this invention B is a seven membered ring andthe optional bond is absent.

In one embodiment of this invention B is an eight membered ring.

In another embodiment of this invention B is an eight membered ring andthe optional bond is present.

In another embodiment of this invention B is an eight membered ring andthe optional bond is absent.

In one embodiment of this invention B is a five membered ring and U isCR⁵.

In another embodiment of this invention B is a five membered ring, U isCR⁵, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, U isCR⁵, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, and U isCR⁵.

In another embodiment of this invention B is a six membered ring, U isCR⁵, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, U isCR⁵, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, and U isCR⁵.

In another embodiment of this invention B is a seven membered ring, U isCR⁵, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, U isCR⁵, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, and Uis CR⁵.

In another embodiment of this invention B is an eight membered ring, Uis CR⁵, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Uis CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring and U isN.

In another embodiment of this invention B is a five membered ring, U isN, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, U isN, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, and U isN.

In another embodiment of this invention B is a six membered ring, U isN, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, U isN, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, and U isN.

In another embodiment of this invention B is a seven membered ring, U isN, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, U isN, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, and Uis N.

In another embodiment of this invention B is an eight membered ring, Uis N, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Uis N, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, U is CR⁵,and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, U isCR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a five membered ring, U isCR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is a six membered ring, and U isCR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, U isCR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a six membered ring, U isCR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is a seven membered ring, U isCR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a seven membered ring, U isCR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a seven membered ring, U isCR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is an eight membered ring, U isCR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is an eight membered ring, Uis CR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is present.

In another embodiment of this invention B is an eight membered ring, Uis CR⁵, there are 1 or 2 heteroatoms present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is a five membered ring, U is N,and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, U isN, there are 1 or 2 additional heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, U isN, there are 1 or 2 additional heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, U is N,and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, U isN, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, U isN, there are 1 or 2 additional heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, U is N,and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a seven membered ring, U isN, there are 1 or 2 additional heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, U isN, there are 1 or 2 additional heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, U is N,and there are 1 or 2 additional heteroatoms present in ring B In anotherembodiment of this invention B is an eight membered ring, U is N, thereare 1 or 2 additional heteroatoms present in ring B, and the optionalbond is present.

In another embodiment of this invention B is an eight membered ring, Uis N, there are 1 or 2 additional heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention G is O.

In another embodiment of this invention G is O and U is CR⁵.

In another embodiment of this invention G is O and U is N.

In another embodiment of this invention G is S.

In another embodiment of this invention G is S and U is CR⁵.

In another embodiment of this invention G is S and U is N.

In one embodiment of this invention G is C(O).

In another embodiment of this invention G is C(O) and U is CR⁵.

In another embodiment of this invention G is C(O) and U is N.

In another embodiment of this invention G is C(O).

In another embodiment of this invention G is C(O) and U is CR⁵.

In another embodiment of this invention G is C(O) and U is N.

In one embodiment of this invention G is N(R¹⁴).

In another embodiment of this invention G is N(R¹⁴) and U is CR⁵.

In another embodiment of this invention G is N(R¹⁴) and U is N.

In one embodiment of this invention G is N(R¹⁴), and R¹⁴ is H (i.e. G isNH).

In another embodiment of this invention G is N(R¹⁴), R¹⁴ is H (i.e. G isNH), and U is CR⁵.

In another embodiment of this invention G is N(R¹⁴), R¹⁴ is H (i.e. G isNH), and U is N.

In one embodiment of this invention B is a five membered ring, and G isO.

In another embodiment of this invention B is a five membered ring, G isO, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isO, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, and G isO.

In another embodiment of this invention B is a six membered ring, G is Oand the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isO, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, and G isO.

In another embodiment of this invention B is a seven membered ring, G isO, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isO, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, and Gis O.

In another embodiment of this invention B is an eight membered ring, Gis O, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis O, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is O,and U is CR⁵.

In another embodiment of this invention B is a five membered ring, G isO, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isO, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is O,and U is CR⁵.

In another embodiment of this invention B is a six membered ring, G isO, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isO, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is O,and U is CR⁵.

In another embodiment of this invention B is a seven membered ring, G isO, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isO, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is O,and U is CR⁵.

In another embodiment of this invention B is an eight membered ring, Gis O, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis O, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is O,and U is N.

In another embodiment of this invention B is a five membered ring, G isO, U is N, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isO, U is N, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is O,and U is N.

In another embodiment of this invention B is a six membered ring, G isO, U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isO, U is N, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is O,and U is N.

In another embodiment of this invention B is a seven membered ring, G isO, U is N, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isO, U is N, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is O,and U is N.

In another embodiment of this invention B is an eight membered ring, Gis O, U is N, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis O, U is N, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is O, Uis CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, G isO, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isO, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G is O,and U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, G isO, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a six membered ring, G isO, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is O,U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

in another embodiment of this invention B is a seven membered ring, G isO, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isO, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is O,U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis O, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis O, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a five membered ring, G is O, Uis N, and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, G isO, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isO, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is O, Uis N, and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, G isO, U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isO, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is O,U is N, and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a seven membered ring, G isO, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isO, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is O,U is N, and there are 1 or 2 additional heteroatoms present in ring B

In another embodiment of this invention B is an eight membered ring, Gis O, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis O, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, and G isS.

In another embodiment of this invention B is a five membered ring, G isS, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isS, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, and G isS.

In another embodiment of this invention B is a six membered ring, G is Sand the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isS, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, and G isS.

In another embodiment of this invention B is a seven membered ring, G isS, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isS, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, and Gis S.

In another embodiment of this invention B is an eight membered ring, Gis S, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis S, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is S,and U is CR⁵.

In another embodiment of this invention B is a five membered ring, G isS, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isS, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is S,and U is CR⁵.

In another embodiment of this invention B is a six membered ring, G isS, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isS, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is S,and U is CR⁵.

In another embodiment of this invention B is a seven membered ring, G isS, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isS, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is S,and U is CR⁵.

In another embodiment of this invention B is an eight membered ring, Gis S, U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis S, U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is S,and U is N.

In another embodiment of this invention B is a five membered ring, G isS, U is N, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isS, U is N, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is S,and U is N.

In another embodiment of this invention B is a six membered ring, G isS, U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isS, U is N, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is S,and U is N.

In another embodiment of this invention B is a seven membered ring, G isS, U is N, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isS, U is N, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is S,and U is N.

In another embodiment of this invention B is an eight membered ring, Gis S, U is N, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis S, U is N, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is S, Uis CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, G isS, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isS, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G is S,and U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, G isS, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a six membered ring, G isS, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is S,U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a seven membered ring, G isS, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isS, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is S,U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis S, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis S, U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a five membered ring, G is S, Uis N, and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, G isS, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isS, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is S, Uis N, and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, G isS, U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isS, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is S,U is N, and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a seven membered ring, G isS, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isS, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is S,U is N, and there are 1 or 2 additional heteroatoms present in ring B

In another embodiment of this invention B is an eight membered ring, Gis S, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis S, U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, and G isC(O).

In another embodiment of this invention B is a five membered ring, G isC(O), and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isC(O), and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, and G isC(O).

In another embodiment of this invention B is a six membered ring, G isC(O) and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isC(O), and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, and G isC(O).

In another embodiment of this invention B is a seven membered ring, G isC(O), and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isC(O), and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, and Gis C(O).

In another embodiment of this invention B is an eight membered ring, Gis C(O), and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis C(O), and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isC(O), and U is CR⁵.

In another embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is C(O),and U is CR⁵.

In another embodiment of this invention B is a six membered ring, G isC(O), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isC(O), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isC(O), and U is CR⁵.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isC(O), and U is CR⁵.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isC(O), and U is N.

In another embodiment of this invention B is a five membered ring, G isC(O), U is N, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isC(O), U is N, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is C(O),and U is N.

In another embodiment of this invention B is a six membered ring, G isC(O), U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isC(O), U is N, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isC(O), and U is N.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is N, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is N, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isC(O), and U is N.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is N, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, G Gis C(O), U is N, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G is C(O),and U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, G isC(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a six membered ring, G isC(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isC(O), U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isC(O), U is N, and there are 1 or 2 additional heteroatoms present inring B.

In another embodiment of this invention B is a five membered ring, G isC(O), U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isC(O), U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is C(O),U is N, and there are 1 or 2 additional heteroatoms present in ring B.

In another embodiment of this invention B is a six membered ring, G isC(O), U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isC(O), U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isC(O), U is N, and there are 1 or 2 additional heteroatoms present inring B.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is N, there are 1 or 2 additional heteroatoms present in ring B,and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isC(O), U is N, and there are 1 or 2 additional heteroatoms present inring B

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is N, there are 1 or 2 additional heteroatoms present in ringB, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is N, there are 1 or 2 additional heteroatoms present in ringB, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, and G isN(R¹⁴).

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, and G isN(R¹⁴).

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴) and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, and G isN(R¹⁴).

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, and Gis N(R¹⁴).

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), and U is CR⁵.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), and U is CR⁵.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), and U is CR⁵.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), and U is CR⁵.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), and U is N.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), and U is N.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), and U is N.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), and U is N.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), and U is CR⁵, and there are 1 or 2 heteroatoms present in ringB.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), U is CR⁵, and there are 1 or 2 heteroatoms present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, there are 1 or 2 heteroatoms present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, and there are 1 or 2 additional heteroatoms present inring B.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, there are 1 or 2 additional heteroatoms present in ringB, and the optional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, there are 1 or 2 additional heteroatoms present in ringB, and the optional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, and there are 1 or 2 additional heteroatoms present inring B.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, and the optional bond is present.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, there are 1 or 2 additional heteroatoms present in ringB, and the optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, and there are 1 or 2 additional heteroatoms present inring B.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, there are 1 or 2 additional heteroatoms present in ringB, and the optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, there are 1 or 2 additional heteroatoms present in ringB, and the optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), U is N, and there are 1 or 2 additional heteroatoms present inring B

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, there are 1 or 2 additional heteroatoms present inring B, and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, there are 1 or 2 additional heteroatoms present inring B, and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is O, Uis CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isO, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a five membered ring, G isO, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is a six membered ring, G is O,and U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isO, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a six membered ring, G isO, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is a seven membered ring, G is O,U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isO, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a seven membered ring, G isO, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is an eight membered ring, G is O,U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis O, U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis O, U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a five membered ring, G is O, Uis N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isO, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isO, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G is O, Uis N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isO, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is O,U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isO, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isO, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is O,U is N, and there is 1 additional heteroatom present in ring B

In another embodiment of this invention B is an eight membered ring, Gis O, U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis O, U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a five membered ring, G is S, Uis CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isS, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a five membered ring, G isS, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is a six membered ring, G is S,and U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isS, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a six membered ring, G isS, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is a seven membered ring, G is S,U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isS, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is present.

In another embodiment of this invention B is a seven membered ring, G isS, U is CR⁵, there is 1 heteroatom present in ring B, and the optionalbond is absent.

In one embodiment of this invention B is an eight membered ring, G is S,U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis S, U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis S, U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a five membered ring, G is S, Uis N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isS, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isS, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G is S, Uis N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isS, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G is S,U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isS, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isS, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G is S,U is N, and there is 1 additional heteroatom present in ring B Inanother embodiment of this invention B is an eight membered ring, G isS, U is N, there is 1 additional heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis S, U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), and U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, there is 1 additional heteroatom present in ring B,and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, there is 1 additional heteroatom present in ring B,and the optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isC(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G is C(O),and U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isC(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a six membered ring, G isC(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isC(O), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a five membered ring, G isC(O), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isC(O), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a five membered ring, G isC(O), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a six membered ring, G is C(O),U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isC(O), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isC(O), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isC(O), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isC(O), U is N, and there is 1 additional heteroatom present in ring B Inanother embodiment of this invention B is an eight membered ring, G isC(O), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis C(O), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), and U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), U is CR⁵, and there is 1 heteroatom present in ring B.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is CR⁵, there is 1 heteroatom present in ring B, and theoptional bond is absent.

In one embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a five membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a six membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is present.

In another embodiment of this invention B is a seven membered ring, G isN(R¹⁴), U is N, there is 1 additional heteroatom present in ring B, andthe optional bond is absent.

In one embodiment of this invention B is an eight membered ring, G isN(R¹⁴), U is N, and there is 1 additional heteroatom present in ring B

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, there is 1 additional heteroatom present in ring B,and the optional bond is present.

In another embodiment of this invention B is an eight membered ring, Gis N(R¹⁴), U is N, there is 1 additional heteroatom present in ring B,and the optional bond is absent.

Other embodiments of this invention are directed to any one of the aboveembodiments wherein G is N(R¹⁴), wherein R¹⁴ is H (i.e. G is NH).

In one embodiment R² (of the NR² moiety) is H.

In another embodiment R² (of the NR² moiety) is alkyl, such as, forexample, methyl, ethyl or isopropyl.

In another embodiment R² (of the NR² moiety) is aryl, such as, forexample, phenyl.

In another embodiment R² (of the NR² moiety) is substituted aryl, suchas, for example, substituted phenyl.

In another embodiment R² (of the NR² moiety) is —C(O)R⁴ wherein R⁴ isalkyl (such as, for example, methyl, ethyl or isopropyl).

In another embodiment R² (of the NR² moiety) is —C(O)R⁴ wherein R⁴ isaryl, such as, for example, phenyl.

In another embodiment R² (of the NR² moiety) is —C(O)R⁴ wherein R⁴ issubstituted aryl, such as, for example, substituted phenyl.

In another embodiment of this invention R⁵ is H.

Another embodiment of this invention is directed to any one of theembodiments above directed to ring (B) wherein U is CR⁵ wherein R⁵ is H.

In another embodiment of this invention ring (B) is not substituted withany R²¹ groups.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and at least one (e.g., 1 to 2) R²¹ is selectedfrom the group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, whereineach R^(15A) is independently selected.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and at least one R²¹ is selected from the groupconsisting of: —SF₅ and —Si(R^(15A))₃, and each R^(15A) is the same ordifferent alkyl group.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and at least one R²¹ is selected from the groupconsisting of: —SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is selected from thegroup consisting of: —SF₅, OSF₅ and —Si(R^(15A))₃.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is selected from thegroup consisting of: —SF₅, OSF₅ and —Si(R^(15A))₃, and each R^(15A) isthe same or different alkyl group.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is selected from thegroup consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are selected from thegroup consisting of: —SF₅, OSF₅ and —Si(R^(15A))₃, wherein each R^(15A)is independently selected.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are selected from thegroup consisting of: —SF₅, OSF₅ and —Si(R^(15A))₃, and each R^(15A) isthe same or different alkyl group.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are selected from thegroup consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and at least one (e.g., 1 to 2) R²¹ is selectedfrom the group consisting of: —SF₅ and —Si(R^(15A))₃, wherein eachR^(15A) is independently selected.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and at least one R²¹ is selected from the groupconsisting of: —SF₅ and —Si(R^(15A))₃, and each R^(15A) is the same ordifferent alkyl group.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and at least one R²¹ is selected from the groupconsisting of: —SF₅ and —Si(CH₃)₃.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is selected from thegroup consisting of: —SF₅ and —Si(R^(15A))₃.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is selected from thegroup consisting of: —SF₅ and —Si(R^(15A))₃, and each R^(15A) is thesame or different alkyl group.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is selected from thegroup consisting of: —SF₅ and —Si(CH₃)₃.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are selected from thegroup consisting of: —SF₅ and —Si(R^(15A))₃, wherein each R^(15A) isindependently selected.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are selected from thegroup consisting of: —SF₅ and —Si(R^(15A))₃, and each R^(15A) is thesame or different alkyl group.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are selected from thegroup consisting of: —SF₅ and —Si(CH₃)₃.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is —SF₅.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are —SF₅.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is —OSF₅.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are —OSF₅.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is —Si(R^(15A))₃.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is —Si(R^(15A))₃ andeach R^(15A) is the same or different alkyl group.

In another embodiment of this invention, there are 1 to 5 R²¹ groupspresent in formula (I), and one of the R²¹ groups is —Si(CH₃)₃.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are the same ordifferent —Si(R^(15A))₃, wherein each R^(15A) is independently selected.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are the same ordifferent —Si(R^(15A))₃ and each R^(15A) is the same or different alkylgroup.

In another embodiment of this invention, there are 2 to 5 R²¹ groupspresent in formula (I), and two of the R²¹ groups are —Si(CH₃)₃.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and at least one (e.g. 1 to 2) of the R²¹ groups is selectedfrom the group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, whereineach R^(15A) is independently selected.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and at least one (e.g. 1 to 2) of the R²¹ groups is selectedfrom the group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, and eachR^(15A) is the same or different alkyl group.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and at least one (e.g. 1 to 2) of the R²¹ groups is selectedfrom the group consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, wherein each R^(15A) is independentlyselected.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, and each R^(15A) is the same or differentalkyl group.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is selected from the group consisting of:—SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two R²¹ groups are selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, wherein each R^(15A) is independentlyselected.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two R²¹ groups are selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, and each R^(15A) is the same or differentalkyl group.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two R²¹ groups are selected from the group consisting of:—SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is —SF₅.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two R²¹ groups are —SF₅.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is —OSF₅.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two R²¹ groups are —OSF₅.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is —Si(R^(15A))₃, wherein each R^(15A) isindependently selected.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is —Si(R^(15A))₃ and each R^(15A) is the sameor different alkyl group.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and one R²¹ group is —Si(CH₃)₃.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two of the R²¹ groups are the same or different—Si(R^(15A))₃, wherein each R^(15A) is independently selected.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two of the R²¹ groups are the same or different —Si(R¹⁵)₃group, and each R^(15A) is the same or different alkyl group.

In another embodiment of this invention R⁷ is substituted with R²¹groups, and two of the R²¹ group are —Si(CH₃)₃.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and at least one (e.g., 1 to 2) R²¹ group is selectedfrom the group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, whereineach R^(15A) is independently selected.

In another embodiment of this invention R⁷ is an aryl group groupsubstituted with R²¹ groups, and at least one (e.g., 1 to 2) R²¹ groupis selected from the group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃,and each R^(15A) is the same or different alkyl group.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and at least one (e.g., 1 to 2) R²¹ group is selectedfrom the group consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and at least one (e.g.,1 to 2) R²¹ group is selected from the group consisting of: —SF₅, —OSF₅and —Si(R^(15A))₃, wherein each R^(15A) is independently selected.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and at least one (e.g.,1 to 2) R²¹ group is selected from the group consisting of: —SF₅, —OSF₅and —Si(R^(15A))₃, and each R^(15A) is the same or different alkylgroup.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and at least one (e.g.,1 to 2) R²¹ group is selected from the group consisting of: —SF₅, —OSF₅and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andat least one (e.g., 1 or 2) R²¹ group on said phenyl is selected fromthe group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, wherein eachR^(15A) is independently selected.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andat least one (e.g., 1 or 2) R²¹ group on said phenyl is selected fromthe group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, and each R^(15A)is the same or different alkyl group.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andat least one (e.g., 1 or 2) R²¹ group on said phenyl is selected fromthe group consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andone R²¹ group on said phenyl is selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, wherein each R^(15A) is independentlyselected.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andone R²¹ group on said phenyl is selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, and each R^(15A) is the same or differentalkyl group.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andone R²¹ group on said phenyl is selected from the group consisting of:—SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3, or 2, or 3) R²¹ groups, andtwo R²¹ groups on said phenyl is selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, wherein each R^(15A) is independentlyselected.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3, or 2, or 3) R²¹ groups, andtwo R²¹ groups on said phenyl is selected from the group consisting of:—SF₅, —OSF₅ and —Si(R^(15A))₃, and each R^(15A) is the same or differentalkyl group.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3, or 2, or 3) R²¹ groups, andtwo R²¹ groups on said phenyl is selected from the group consisting of:—SF₅, —OSF₅ and —Si(CH₃)₃.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andone R²¹ group on said phenyl is —SF₅.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andone R²¹ group on said phenyl is —OSF₅.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andone R²¹ group on said phenyl is —Si(R^(15A))₃, wherein each R^(15A) isindependently selected.

In another embodiment of this invention R⁷ is an aryl group groupsubstituted with R²¹ groups, and said aryl moiety is phenyl, and saidphenyl is substituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹group, and one R²¹ group on said phenyl is —Si(R^(15A))₃, and eachR^(15A) is the same or different alkyl group.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least one (e.g., 1 to 3, or 1 to 2) R²¹ group, andone R²¹ group on said phenyl is —Si(CH₃)₃.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3) R²¹ groups, and two of theR²¹ groups on said phenyl are —SF₅.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3) R²¹ groups, and two of theR²¹ groups on said phenyl are —OSF₅.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3) R²¹ groups, and two of theR²¹ groups on said phenyl are —Si(R^(15A))₃, wherein each R^(15A) isindependently selected.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3) R²¹ groups, and two of theR²¹ groups on said phenyl are —Si(R^(15A))₃, and each R^(15A) is thesame or different alkyl group.

In another embodiment of this invention R⁷ is an aryl group substitutedwith R²¹ groups, and said aryl moiety is phenyl, and said phenyl issubstituted with at least two (e.g., 2 to 3) R²¹ groups, and two of theR²¹ groups on said phenyl are —Si(CH₃)₃.

In another embodiment of this invention R⁶ is alkyl.

In another embodiment of this invention R⁶ is a C₁ to C₃ alkyl group.

In another embodiment of this invention R⁶ is methyl.

In another embodiment of this invention R⁶ is ethyl.

In another embodiment of this invention R⁶ is a C₃ alkyl group.

In another embodiment of this invention R⁶ is isopropyl.

In another embodiment R⁶ is —C(O)OR¹⁵.

In another embodiment R⁶ is —C(O)OR¹⁵ wherein R¹⁵ is alkyl.

In another embodiment R⁶ is —C(O)OR¹⁵ wherein R¹⁵ is methyl.

In another embodiment R⁶ is alkyl substituted with 1-5 R²¹ groups.

In another embodiment R⁶ is alkyl substituted with one R²¹ group.

In another embodiment R⁶ is alkyl substituted with one R²¹ group, andsaid R²¹ group is —OR¹⁵.

In another embodiment R⁶ is alkyl substituted with one R²¹ group, andsaid R²¹ group is —OR¹⁵, and said R¹⁵ is alkyl.

In another embodiment R⁶ is alkyl substituted with one R²¹ group, andsaid R²¹ group is —OR¹⁵, and said R¹⁵ is methyl.

In another embodiment R⁶ is —CH₂R²¹ (i.e. alkyl substituted with one R²¹group, wherein said alkyl is —CH₂—).

In another embodiment R⁶ is —CH₂OR¹⁵ (i.e. alkyl substituted with oneR²¹ group, wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵).

In another embodiment R⁶ is —CH₂OR¹⁵ (i.e. alkyl substituted with oneR²¹ group, wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),wherein said R¹⁵ group is alkyl.

In another embodiment R⁶ is —CH₂OR¹⁵ (i.e. alkyl substituted with oneR²¹ group, wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),wherein said R¹⁵ group is methyl.

In another embodiment R⁶ is —C(O)NR¹⁵R¹⁶.

In another embodiment R⁶ is —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are eachindependently selected from the group consisting of: H and alkyl.

In another embodiment R⁶ is —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are thesame or different alkyl.

In another embodiment R⁶ is —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are eachindependently selected from the group consisting of: H and methyl.

In another embodiment R⁶ is —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are eachmethyl.

Other embodiments of this invention are directed to any one of theembodiments above directed to Ring (B) wherein R⁶ is alkyl. In one suchembodiment R⁶ is a C₁ to C₃ alkyl group. In another embodiment R⁶ ismethyl. In another embodiment R⁶ is ethyl. In another embodiment R⁶ is aC₃ alkyl group. In another embodiment R⁶ is isopropyl.

In another embodiment of this invention R⁷ is an unsubstituted arylgroup (e.g., an unsubstituted phenyl group). Thus, in another embodimentR⁷ is phenyl.

In another embodiment of this invention R⁷ is a substituted aryl group(e.g., a substituted phenyl group). Thus, in another embodiment R⁷ is asubstituted phenyl group.

In another embodiment of this invention R⁷ is an aryl group substitutedwith 1 to 3 independently selected R²¹ groups.

In another embodiment of this invention R⁷ is an aryl group substitutedwith one to 3 R²¹ groups, and each R²¹ group is the same or differenthalo.

In another embodiment of this invention R⁷ is an aryl group substitutedwith one to 3 R²¹ groups, and each R²¹ group is F.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with one or more independently selected R²¹ groups.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with 1 to 3 independently selected R²¹ groups.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with 1 or 2 independently selected R²¹ groups.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with 1 R²¹ group.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with 1 to 3 R²¹ groups, and each R²¹ group is the same ordifferent halo.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with three R²¹ halo groups, and each R²¹ group is the sameor different halo.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with two R²¹ halo groups, and each R²¹ group is the same ordifferent halo.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with one R²¹ halo group.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with 1 to 3 F (i.e., said phenyl is substituted with 1 to 3R²¹ groups, and said R²¹ groups are halo, and said halo is F).

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with one F (i.e., said phenyl is substituted with one R²¹group, and said R²¹ group is halo, and said halo is F).

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with two F atoms (i.e., said phenyl is substituted with twoR²¹ groups, and said R²¹ groups are halo, and said halo is F).

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with three F atoms (i.e., said phenyl is substituted withthree R²¹ groups, and said R²¹ groups are halo, and said halo is F).

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with one —CN group.

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with one or two R²¹ alkyl groups (e.g. methyl groups),wherein each R²¹ group is substituted with 1 to 3 R²² halo groups (e.g.F groups).

In another embodiment of this invention R⁷ is phenyl, and said phenyl issubstituted with one or two —CF₃ groups (i.e. there are one or two R²¹alkyl groups (i.e. methyl groups) each substituted with 3 R²² halo (i.e.F) groups).

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

In another embodiment of this invention R⁷ is:

Other embodiments of this invention are directed to any one of theembodiments above directed to Ring (B) wherein:

-   -   (a) R⁶ is:        -   (1) alkyl, or        -   (2) C₁ to C₃ alkyl, or        -   (3) methyl, or        -   (4) ethyl, or        -   (5) a C₃ alkyl group, or        -   (6) isopropyl, or        -   (7) —C(O)OR¹⁵, or        -   (8) —C(O)OR¹⁵ wherein R¹⁵ is alkyl, or        -   (9) —C(O)OR¹⁵ wherein R¹⁵ is methyl, or        -   (10) alkyl substituted with 1-5 R²¹ groups, or        -   (11) alkyl substituted with one R²¹ group, or        -   (12) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, or        -   (13) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, and said R¹⁵ is alkyl, or        -   (14) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, and said R¹⁵ is methyl, or        -   (15) —CH₂R²¹ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—), or        -   (16) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            or        -   (17) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            wherein said R¹⁵ group is alkyl, or        -   (18) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            wherein said R¹⁵ group is methyl, or        -   (19) —C(O)NR¹⁵R¹⁶, or        -   (20) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each independently            selected from the group consisting of: H and alkyl, or        -   (21) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are the same or            different alkyl, or        -   (22) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each independently            selected from the group consisting of: H and methyl, or        -   (23) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each methyl; and    -   (b) R⁷ is as defined in any one of the embodiments above that        are directed to R⁷.

Other embodiments of this invention are directed to any one of theembodiments above directed to Ring (B) wherein:

-   -   (a) R⁶ is:        -   (1) alkyl, or        -   (2) C₁ to C₃ alkyl, or        -   (3) methyl, or        -   (4) ethyl, or        -   (5) a C₃ alkyl group, or        -   (6) isopropyl, or        -   (7) —C(O)OR¹⁵, or        -   (8) —C(O)OR¹⁵ wherein R¹⁵ is alkyl, or        -   (9) —C(O)OR¹⁵ wherein R¹⁵ is methyl, or        -   (10) alkyl substituted with 1-5 R²¹ groups, or        -   (11) alkyl substituted with one R²¹ group, or        -   (12) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, or        -   (13) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, and said R¹⁵ is alkyl, or        -   (14) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, and said R¹⁵ is methyl, or        -   (15) —CH₂R²¹ (i.e, alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—), or        -   (16) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            or        -   (17) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            wherein said R¹⁵ group is alkyl, or        -   (18) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            wherein said R¹⁵ group is methyl, or        -   (19) —C(O)NR¹⁵R¹⁶, or        -   (20) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each independently            selected from the group consisting of: H and alkyl, or        -   (21) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are the same or            different alkyl, or        -   (22) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each independently            selected from the group consisting of: H and methyl, or        -   (23) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each methyl; and    -   (b) R⁷ is selected from the group consisting of:

Other embodiments of this invention are directed to any one of theembodiments above directed to Ring (B) wherein:

-   -   (a) R⁶ is:        -   (1) alkyl, or        -   (2) C₁ to C₃ alkyl, or        -   (3) methyl, or        -   (4) ethyl, or        -   (5) a C₃ alkyl group, or        -   (6) isopropyl, or        -   (7) —C(O)OR¹⁵, or        -   (8) —C(O)OR¹⁵ wherein R¹⁵ is alkyl, or        -   (9) —C(O)OR¹⁵ wherein R¹⁵ is methyl, or        -   (10) alkyl substituted with 1-5 R²¹ groups, or        -   (11) alkyl substituted with one R²¹ group, or        -   (12) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, or        -   (13) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, and said R¹⁵ is alkyl, or        -   (14) alkyl substituted with one R²¹ group, and said R²¹            group is —OR¹⁵, and said R¹⁵ is methyl, or        -   (15) —CH₂R²¹ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—), or        -   (16) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            or        -   (17) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            wherein said R¹⁵ group is alkyl, or        -   (18) —CH₂OR¹⁵ (i.e. alkyl substituted with one R²¹ group,            wherein said alkyl is —CH₂—, and said R²¹ group is —OR¹⁵),            wherein said R¹⁵ group is methyl, or        -   (19) —C(O)NR¹⁵R¹⁶, or        -   (20) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each independently            selected from the group consisting of: H and alkyl, or        -   (21) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are the same or            different alkyl, or        -   (22) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each independently            selected from the group consisting of: H and methyl, or        -   (23) —C(O)NR¹⁵R¹⁶ wherein R¹⁵ and R¹⁶ are each methyl; and    -   (b) R⁷ is selected from the group consisting of:

Other embodiments of this invention are directed to any one of theembodiments above directed to Ring (B) wherein R⁶ is alkyl and R⁷ is asdefined in any one of the above embodiments directed to R⁷. In one suchembodiment R⁶ is a C₁ to C₃ alkyl group. In another embodiment R⁶ ismethyl. In another embodiment R⁶ is ethyl. In another embodiment R⁶ is aC₃ alkyl group. In another embodiment R⁶ is isopropyl.

In another embodiment of this invention R¹⁰ is selected from the groupconsisting of aryl and aryl substituted with one or more R²¹ groups.

In another embodiment of this invention R⁹ is selected from the groupconsisting of heteroaryl and heteroaryl substituted with one or more R²¹groups, and wherein each R²¹ is independently selected.

In another embodiment of this invention R¹⁰ is selected from the groupconsisting of aryl and aryl substituted with one or more R²¹ groups, andR⁹ is selected from the group consisting of heteroaryl and heteroarylsubstituted with one or more R²¹ groups, and wherein each R²¹ isindependently selected.

Other embodiments of this invention are directed to any one of theembodiments above directed to Ring (B) wherein R⁶ is alkyl, R⁷ is asdefined in any one of the above embodiments directed to R⁷, R¹⁰ isselected from the group consisting of aryl and aryl substituted with oneor more independently selected R²¹ groups, and R⁹ is selected from thegroup consisting of heteroaryl and heteroaryl substituted with one ormore independently selected R²¹ groups. In one such embodiment R⁶ is aC₁ to C₃ alkyl group. In another embodiment R⁶ is methyl. In anotherembodiment R⁶ is ethyl. In another embodiment R⁶ is a C₃ alkyl group. Inanother embodiment R⁶ is isopropyl.

In another embodiment of this invention R¹⁰ is heteroaryl (e.g.pyridyl).

In another embodiment of this invention R¹⁰ is heteroaryl substitutedwith one or more R²¹ groups (e.g. pyridyl substituted with one or moreR²¹ groups).

In another embodiment of this invention R¹⁰ is selected from the groupconsisting of heteroaryl and heteroaryl substituted with one or more R²¹groups, and R⁹ group is selected from the group consisting of heteroaryland heteroaryl substituted with one or more R²¹ groups, and wherein eachR²¹ is independently selected.

Other embodiments of this invention are directed to the compounds offormula (I) wherein R¹⁰ is heteroaryl or heteroaryl substituted with oneor more R²¹ groups, and R⁹ is heteroaryl (e.g., imidazolyl) orheteroaryl (e.g., imidazolyl) substituted with one or more (e.g., one ortwo, or one) R²¹ groups (e.g., alkyl, such as, for example, methyl).

Other embodiments of this invention are directed to any one of theembodiments above directed to Ring (B) wherein R⁶ is alkyl, R⁷ is asdefined in any one of the above embodiments directed to R⁷, R¹⁰ isselected from the group consisting of heteroaryl and heteroarylsubstituted with one or more independently selected R²¹ groups, and R⁹is selected from the group consisting of heteroaryl and heteroarylsubstituted with one or more independently selected R²¹ groups. In onesuch embodiment R⁶ is a C₁ to C₃ alkyl group. In another embodiment R⁶is methyl.

In another embodiment R⁶ is ethyl. In another embodiment R⁶ is a C₃alkyl group. In another embodiment R⁶ is isopropyl.

In another embodiment of this invention R¹⁰ is aryl.

In another embodiment of this invention R¹⁰ aryl is aryl and said arylis phenyl.

In another embodiment of this invention R¹⁰ is aryl substituted with oneor more R²¹ groups.

In another embodiment of this invention R¹⁰ is aryl substituted with oneor more R²¹ groups, and said aryl is phenyl, i.e., said R¹⁰ group isphenyl substituted with one or more R²¹ groups.

In another embodiment of this invention R¹⁰ is phenyl substituted withone or more R²¹ groups, and each R²¹ group is the same or different—OR¹⁵ group.

In another embodiment of this invention R¹⁰ is phenyl substituted withone or more R²¹ groups, and each R²¹ group is the same or different—OR¹⁵ group, and said R¹⁵ is alkyl, and each alkyl is independentlyselected.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group, and said R²¹ group is —OR¹⁵, and said R¹⁵ is alkyl.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group, and said R²¹ group is —OR¹⁵, and said R¹⁵ is alkyl, andsaid alkyl is methyl.

In another embodiment of this invention R¹⁰ is phenyl substituted withone or more (e.g., one or two, or one) independently selected R²¹ halogroups.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group, and said R²¹ group is halo.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group, and said R²¹ group is F.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group and said R²¹ is an —OR¹⁵ group, and R¹⁵ is an(R¹⁸)_(n)alkyl group, and R¹⁸ is halo, and n is 1 to 3, and each halo isindependently selected.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group and said R²¹ is an —OR¹⁵ group, and R¹⁵ is an(R¹⁸)_(n)alkyl group, and R¹⁸ is F, and n is 3.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group and said R²¹ is an —OR¹⁵ group, and R¹⁵ is an(R¹⁸)_(n)alkyl group, and R¹⁸ is F, and n is 3, and the alkyl is methyl(i.e., the R²¹ substituent is —OCF₃).

In another embodiment of this invention R⁹ is heteroaryl.

In another embodiment of this invention R⁹ is heteroaryl substitutedwith one or more R²¹ groups.

In another embodiment of this invention R⁹ is heteroaryl substitutedwith one or more R²¹ groups, and said R²¹ groups are the same ordifferent alkyl.

In another embodiment of this invention R⁹ is heteroaryl substitutedwith one R²¹ group, and said R²¹ is alkyl.

In another embodiment of this invention R⁹ is heteroaryl substitutedwith one R²¹ group, and said R²¹ is alkyl, and said alkyl is methyl.

In another embodiment of this invention R⁹ is and said heteroaryl isimidazoyl.

In another embodiment of this invention R⁹ is imidazolyl substitutedwith one or more R²¹ groups.

In another embodiment of this invention R⁹ is imidazolyl substitutedwith one or more R²¹ groups, and said R²¹ groups are the same ordifferent alkyl.

In another embodiment of this invention R⁹ is imidazolyl substitutedwith one R²¹ group, and said R²¹ is alkyl.

In another embodiment of this invention R⁹ is imidazolyl substitutedwith one R²¹ group, and said R²¹ is alkyl, and said alkyl is methyl.

In another embodiment of this invention R¹⁰ is selected from the groupconsisting of aryl and aryl substituted with one or more R²¹ groups, andsaid R⁹ group is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more R²¹ groups, wherein each R²¹ isindependently selected.

In another embodiment of this invention R¹⁰ is phenyl substituted withone or more R²¹ groups, and said R⁹ is imidazolyl substituted with oneor more R²¹ groups, wherein each R²¹ is independently selected.

In another embodiment of this invention R¹⁰ is phenyl substituted withone R²¹ group, and said R⁹ is imidazolyl substituted with one R²¹ group,wherein each R²¹ is independently selected.

In another embodiment of this invention R¹⁰ is phenyl substituted withone or more independently selected —OR¹⁵ groups, and said R⁹ isimidazolyl substituted with one or more independently selected alkylgroups.

In another embodiment of this invention R¹⁰ is phenyl substituted withone or more independently selected —OR¹⁵ groups, and said R⁹ isimidazolyl substituted with one or more independently selected alkylgroups, and each R¹⁵ is the same or different alkyl group.

In another embodiment of this invention R¹⁰ is phenyl substituted withone —OR¹⁵ group, and said R⁹ is imidazolyl substituted with one alkylgroup.

In another embodiment of this invention R¹⁰ is phenyl substituted withone —OR¹⁵ group, and said R⁹ is imidazolyl substituted with one alkylgroup, and R¹⁵ is alkyl, and wherein the R¹⁵ alkyl group, and the alkylgroup on said imidazolyl are independently selected.

In another embodiment of this invention R¹⁰ is phenyl substituted withone —OR¹⁵ group, and said R⁹ is imidazolyl substituted with one methylgroup, and R¹⁵ is methyl, and wherein the R¹⁵ alkyl group, and the alkylgroup on said imidazolyl are independently selected.

Other embodiments of the compounds of formula (I) are directed to anyone of the above embodiments wherein R⁹ is:

Other embodiments of the compounds of formula (I) are directed to anyone of the above embodiments wherein R⁹ is:

Other embodiments of the compounds of formula (I) are directed to anyone of the above embodiments wherein R¹⁰ is:

(wherein the —OR¹⁵ is ortho to the carbon to which R⁹ is bound to, i.e.,the R⁹—R¹⁰— moiety is:

Other embodiments for the compounds of formula (I) are directed to anyone of the above embodiments wherein R¹⁰ is:

(wherein the —OCH₃ is ortho to the carbon to which R⁹ is bound to, i.e.,the R⁹—R¹⁰— moiety is:

In another embodiment of this invention the R⁹—R¹⁰— moiety is:

In another embodiment of this invention the R⁹—R¹⁰— moiety is:

In another embodiment of this invention the R⁹—R¹⁰— moiety is:

In another embodiment of this invention the R⁹—R¹⁰— moiety is:

In another embodiment of this invention the R⁹— R¹⁰— moiety is:

In another embodiment of this invention the R⁹—R¹⁰— moiety is:

In another embodiment of this invention the R⁹—R¹⁰— moiety is:

In another embodiment of this invention the R⁹—R¹⁰— moiety is:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is selected from the group consisting of:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is selected from the group consisting of:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is selected from the group consisting of:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is selected from the group consisting of:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is selected from the group consisting of:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is:

In another embodiment of this invention R⁷ is selected from the groupconsisting of:

the R⁹—R¹⁰— moiety is:

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is an aryl group, or R⁷ is an aryl group substituted with 1 to 3independently selected R²¹ groups, (c) R¹⁰ is selected from the groupconsisting of aryl and aryl substituted with one or more independentlyselected R²¹ groups, and (d) R⁹ is selected from the group consisting ofheteroaryl and heteroaryl substituted with one or more independentlyselected R²¹ groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofaryl and aryl substituted with one or more independently selected R²¹groups, and (d) R⁹ is selected from the group consisting of heteroaryland heteroaryl substituted with one or more independently selected R²¹groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, and (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or more independentlyselected R²¹ groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, and (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or more independentlyselected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 2 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 R²¹ halo group, (c)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is alkyl, and (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷is phenyl substituted with 1 to 3 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷is phenyl substituted with 1 to 2 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 F (i.e., R⁷ isphenyl substituted with 1 R²¹ group, and said R²¹ group is halo, andsaid halo is F), (b) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of aryl and arylsubstituted with one or more independently selected R²¹ groups, and (d)R⁹ is selected from the group consisting of heteroaryl and heteroarylsubstituted with one or more independently selected R²¹ groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected R²¹ groups,and (d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected R²¹groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected —OR¹⁵ groups,and (d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected alkylgroups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 2 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or two independently selected —OR¹⁵ groups,wherein R¹⁵ is alkyl, and (d) R⁹ is selected from the group consistingof imidazolyl and imidazolyl substituted with one or two independentlyselected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 R²¹ halo group, (c) R¹⁰ is selectedfrom the group consisting of phenyl and phenyl substituted with one ortwo independently selected —OR¹⁵ groups, wherein R¹⁵ is alkyl, and (d)R⁹ is selected from the group consisting of imidazolyl and imidazolylsubstituted with one or two independently selected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷ is phenylsubstituted with 1 to 3 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷ is phenylsubstituted with 1 to 2 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 F (i.e., R⁷ is phenyl substitutedwith 1 R²¹ group, and said R²¹ group is halo, and said halo is F), (b)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is methyl, and (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting of aryland aryl substituted with one or more independently selected R²¹ groups,and (d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, and (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or more independentlyselected R²¹ groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, and (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or more independentlyselected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected alkyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (b) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, and (d) R⁹ is selected from thegroup consisting of imidazolyl and imidazolyl substituted with one ortwo independently selected methyl groups.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is an aryl group, or R⁷ is an aryl group substituted with 1 to 3independently selected R²¹ groups, (c) R¹⁶ is selected from the groupconsisting of aryl and aryl substituted with one or more independentlyselected R²¹ groups, (d) R⁹ is selected from the group consisting ofheteroaryl and heteroaryl substituted with one or more independentlyselected R²¹ groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofaryl and aryl substituted with one or more independently selected R²¹groups, (d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 2 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups groups, (e) and G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 R²¹ halo group, (c)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is alkyl, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or two independently selected alkylgroups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷is phenyl substituted with 1 to 3 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷is phenyl substituted with 1 to 2 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 F (i.e., R⁷ isphenyl substituted with 1 R²¹ group, and said R²¹ group is halo, andsaid halo is F), (b) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of aryl and arylsubstituted with one or more independently selected R²¹ groups, (d) R⁹is selected from the group consisting of heteroaryl and heteroarylsubstituted with one or more independently selected R²¹ groups, and (e)G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected R²¹groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected —OR¹⁵ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 2 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or two independently selected —OR¹⁵ groups,wherein R¹⁵ is alkyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected alkyl groups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 R²¹ halo group, (c) R¹⁰ is selectedfrom the group consisting of phenyl and phenyl substituted with one ortwo independently selected —OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ isselected from the group consisting of imidazolyl and imidazolylsubstituted with one or two independently selected alkyl groups groups,and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷ is phenylsubstituted with 1 to 3 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷ is phenylsubstituted with 1 to 2 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 F (i.e., R⁷ is phenyl substitutedwith 1 R²¹ group, and said R²¹ group is halo, and said halo is F), (b)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is methyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected methyl groups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting of aryland aryl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (b) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is O.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is an aryl group, or R⁷ is an aryl group substituted with 1 to 3independently selected R²¹ groups, (c) R¹⁰ is selected from the groupconsisting of aryl and aryl substituted with one or more independentlyselected R²¹ groups, (d) R⁹ is selected from the group consisting ofheteroaryl and heteroaryl substituted with one or more independentlyselected R²¹ groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofaryl and aryl substituted with one or more independently selected R²¹groups, (d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ halo groups, (c) R¹⁶ is selected from the group consistingof phenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 2 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups groups, (e) and G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 R²¹ halo group, (c)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is alkyl, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or two independently selected alkylgroups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷is phenyl substituted with 1 to 3 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷is phenyl substituted with 1 to 2 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 F (i.e., R⁷ isphenyl substituted with 1 R²¹ group, and said R²¹ group is halo, andsaid halo is F), (b) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of aryl and arylsubstituted with one or more independently selected R²¹ groups, (d) R⁹is selected from the group consisting of heteroaryl and heteroarylsubstituted with one or more independently selected R²¹ groups, and (e)G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected R²¹groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected —OR¹⁵ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 2 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or two independently selected —OR¹⁵ groups,wherein R¹⁵ is alkyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected alkyl groups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 R²¹ halo group, (c) R¹⁰ is selectedfrom the group consisting of phenyl and phenyl substituted with one ortwo independently selected —OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ isselected from the group consisting of imidazolyl and imidazolylsubstituted with one or two independently selected alkyl groups groups,and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷ is phenylsubstituted with 1 to 3 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷ is phenylsubstituted with 1 to 2 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 F (i.e., R⁷ is phenyl substitutedwith 1 R²¹ group, and said R²¹ group is halo, and said halo is F), (b)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is methyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected methyl groups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting of aryland aryl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁶ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁶ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (b) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is S.

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is an aryl group, or R⁷ is an aryl group substituted with 1 to 3independently selected R²¹ groups, (c) R¹⁰ is selected from the groupconsisting of aryl and aryl substituted with one or more independentlyselected R²¹ groups, (d) R⁹ is selected from the group consisting ofheteroaryl and heteroaryl substituted with one or more independentlyselected R²¹ groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁶ is selected from the group consisting ofaryl and aryl substituted with one or more independently selected R²¹groups, (d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 2 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups groups, (e) and G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 R²¹ halo group, (c)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is alkyl, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or two independently selected alkylgroups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷is phenyl substituted with 1 to 3 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷is phenyl substituted with 1 to 2 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 F (i.e., R⁷ isphenyl substituted with 1 R²¹ group, and said R²¹ group is halo, andsaid halo is F), (b) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of aryl and arylsubstituted with one or more independently selected R²¹ groups, (d) R⁹is selected from the group consisting of heteroaryl and heteroarylsubstituted with one or more independently selected R²¹ groups, and (e)G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected R²¹groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected —OR¹⁵ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 2 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or two independently selected —OR¹⁵ groups,wherein R¹⁵ is alkyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected alkyl groups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 R²¹ halo group, (c) R¹⁰ is selectedfrom the group consisting of phenyl and phenyl substituted with one ortwo independently selected —OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ isselected from the group consisting of imidazolyl and imidazolylsubstituted with one or two independently selected alkyl groups groups,and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷ is phenylsubstituted with 1 to 3 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷ is phenylsubstituted with 1 to 2 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 F (i.e., R⁷ is phenyl substitutedwith 1 R²¹ group, and said R²¹ group is halo, and said halo is F), (b)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is methyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected methyl groups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting of aryland aryl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (b) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is C(O).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is an aryl group, or R⁷ is an aryl group substituted with 1 to 3independently selected R²¹ groups, (c) R¹⁰ is selected from the groupconsisting of aryl and aryl substituted with one or more independentlyselected R²¹ groups, (d) R⁹ is selected from the group consisting ofheteroaryl and heteroaryl substituted with one or more independentlyselected R²¹ groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofaryl and aryl substituted with one or more independently selected R²¹groups, (d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ groups, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 3 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 to 2 independentlyselected R²¹ halo groups, (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups groups, (e) and G is N(R¹⁴) (and inone example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl substituted with 1 R²¹ halo group, (c)R¹⁰ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is alkyl, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or two independently selected alkylgroups groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷is phenyl substituted with 1 to 3 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is N(R¹⁴) (and inone example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷is phenyl substituted with 1 to 2 R²¹ groups, and said R²¹ groups arehalo, and said halo is F), (c) R¹⁰ is selected from the group consistingof phenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is N(R¹⁴) (and inone example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, or R⁷ is phenyl, substituted with 1 F (i.e., R⁷ isphenyl substituted with 1 R²¹ group, and said R²¹ group is halo, andsaid halo is F), (b) R¹⁶ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups groups, and (e) G is N(R¹⁴) (and inone example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁶ is selected from the group consisting of aryl and arylsubstituted with one or more independently selected R²¹ groups, (d) R⁹is selected from the group consisting of heteroaryl and heteroarylsubstituted with one or more independently selected R²¹ groups, and (e)G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹groups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected R²¹groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 3 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or more independently selected —OR¹⁵ groups,(d) R⁹ is selected from the group consisting of imidazolyl andimidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 to 2 independently selected R²¹ halogroups, (c) R¹⁰ is selected from the group consisting of phenyl andphenyl substituted with one or two independently selected —OR¹⁵ groups,wherein R¹⁵ is alkyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected alkyl groups groups, and (e) G is N(R¹⁴) (and in one example Gis NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl substituted with 1 R²¹ halo group, (c) R¹⁰ is selectedfrom the group consisting of phenyl and phenyl substituted with one ortwo independently selected —OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ isselected from the group consisting of imidazolyl and imidazolylsubstituted with one or two independently selected alkyl groups groups,and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 3 F (i.e., R⁷ is phenylsubstituted with 1 to 3 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is N(R¹⁴) (and in oneexample G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 to 2 F (i.e., R⁷ is phenylsubstituted with 1 to 2 R²¹ groups, and said R²¹ groups are halo, andsaid halo is F), (c) R¹⁰ is selected from the group consisting of phenyland phenyl substituted with one or two independently selected —OR¹⁵groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is N(R¹⁴) (and in oneexample G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, substituted with 1 F (i.e., R⁷ is phenyl substitutedwith 1 R²¹ group, and said R²¹ group is halo, and said halo is F), (b)R¹⁶ is selected from the group consisting of phenyl and phenylsubstituted with one or two independently selected —OR¹⁵ groups, whereinR¹⁵ is methyl, (d) R⁹ is selected from the group consisting ofimidazolyl and imidazolyl substituted with one or two independentlyselected methyl groups groups, and (e) G is N(R¹⁴) (and in one example Gis NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting of aryland aryl substituted with one or more independently selected R²¹ groups,(d) R⁹ is selected from the group consisting of heteroaryl andheteroaryl substituted with one or more independently selected R²¹groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selectedR²¹ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected R²¹groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or more independently selected—OR¹⁵ groups, (d) R⁹ is selected from the group consisting of imidazolyland imidazolyl substituted with one or more independently selected alkylgroups groups, and (e) G is N(R¹⁴) (and in one example G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is N(R¹⁴) (and in oneexample G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is alkyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected alkyl groups, and (e) G is N(R¹⁴) (and in oneexample G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is N(R¹⁴) (and in oneexample G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (c) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is N(R¹⁴) (and in oneexample G is NH).

In another embodiment of this invention: (a) R⁶ is alkyl (e.g., methyl),(b) R⁷ is phenyl, (b) R¹⁰ is selected from the group consisting ofphenyl and phenyl substituted with one or two independently selected—OR¹⁵ groups, wherein R¹⁵ is methyl, (d) R⁹ is selected from the groupconsisting of imidazolyl and imidazolyl substituted with one or twoindependently selected methyl groups, and (e) G is N(R¹⁴) (and in oneexample G is NH).

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinring B is as defined in any one of the embodiments directed to ring Babove.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present and U is N.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is N, and ring B is a 5membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is N, and ring B is a 6membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is N, and ring B is a 7membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present and U is CR⁵.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is CR⁵, and ring B is a 5membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is CR⁵, and ring B is a 6membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is CR⁵, and ring B is a 7membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is CR⁵ and R⁵ is H.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is CR⁵ and R⁵ is H, and ring Bis a 5 membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is CR⁵ and R⁵ is H, and ring Bis a 6 membered ring.

Other embodiments of this invention are directed to the aboveembodiments (which are directed to the combination of R⁶, and R⁷, andR¹⁰, and R⁹, with G being O, C(O), N(R¹⁴) (such as NH), or S) whereinthe optional bond in ring B is present, U is CR⁵ and R⁵ is H, and ring Bis a 7 membered ring.

Other embodiments of this invention are directed to any one of theembodiments above wherein ring B is substituted with 1 or two R²¹groups. In one example each R²¹ group is the same or different alkylgroup. In another example each R²¹ is methyl. In another example ring Bis substituted with two R²¹ groups. In another example ring B issubstituted with two R²¹ groups and each group is the same or differentalkyl group. In another example ring B is substituted with two R²¹groups and each group is methyl group. In another example ring B issubstituted with one R²¹ group. In another example ring B is substitutedwith one R²¹ group and said R²¹ group is alkyl. In another example ringB is substituted with one R²¹ group and said R²¹ group is alkyl and saidalkyl group is methyl.

In another embodiment of this invention ring B is substituted with 1 ortwo R²¹ groups.

In another embodiment of this invention ring B is substituted with 1 or2 R²¹ groups wherein each R²¹ group is the same or different alkylgroup.

In another embodiment of this invention ring B is substituted with 1 or2 R²¹ groups wherein each R²¹ group is methyl.

In another embodiment of this invention ring B is substituted with twoR²¹ groups.

In another embodiment of this invention ring B is substituted with twoR²¹ groups wherein each R²¹ group is the same or different alkyl group.

In another embodiment of this invention ring B is substituted with twoR²¹ groups and each R²¹ group is methyl.

In another embodiment of this invention ring B is substituted with oneR²¹ group.

In another embodiment of this invention ring B is substituted with oneR²¹ group wherein said R²¹ group is an alkyl group.

In another embodiment of this invention ring B is substituted with oneR²¹ group and said R²¹ group is methyl.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the croup consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, and R¹⁰, are as defined for formula (I) or anyof the embodiments thereof.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, and R¹⁰, are as defined for formula (I) or anyof the embodiments thereof.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹⁴ and R²¹ are as defined for formula (I)or any of the embodiments thereof. In one example of this embodimentthere are 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there isone R²¹ group, or there are two independently selected R²¹ groups) inring B. In another example of this embodiment there are twoindependently selected R²¹ groups in ring B. In another example of thisembodiment there is one R²¹ group in ring B. In one example of thisembodiment there are 0 to 2 R²¹ groups in ring B wherein said R²¹ groupsare the same or different alkyl groups (e.g. methyl). In another exampleof this embodiment there are two independently selected R²¹ groups inring B wherein each R²¹ group is the same or different alkyl group(e.g., methyl). In another example of this embodiment there is one R²¹group and said R²¹ group is alkyl (e.g. methyl). In another example ofthis embodiment there are no R²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹⁴ and R²¹ are as defined for formula (I)or any of the embodiments thereof. In one example of this embodimentthere are 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there isone R²¹ group, or there are two independently selected R²¹ groups) inring B. In another example of this embodiment there are twoindependently selected R²¹ groups in ring B. In another example of thisembodiment there is one R²¹ group in ring B. In one example of thisembodiment there are 0 to 2 R²¹ groups in ring B wherein said R²¹ groupsare the same or different alkyl groups (e.g. methyl). In another exampleof this embodiment there are two independently selected R²¹ groups inring B wherein each R²¹ group is the same or different alkyl group(e.g., methyl). In another example of this embodiment there is one R²¹group and said R²¹ group is alkyl (e.g. methyl). In another example ofthis embodiment there are no R²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, R¹⁴ and R²¹ are as defined for formula (I)or any of the embodiments thereof. In one example of this embodimentthere are 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there isone R²¹ group, or there are two independently selected R²¹ groups) inring B. In another example of this embodiment there are twoindependently selected R²¹ groups in ring B. In another example of thisembodiment there is one R²¹ group in ring B. In one example of thisembodiment there are 0 to 2 R²¹ groups in ring B wherein said R²¹ groupsare the same or different alkyl groups (e.g. methyl). In another exampleof this embodiment there are two independently selected R²¹ groups inring B wherein each R²¹ group is the same or different alkyl group(e.g., methyl). In another example of this embodiment there is one R²¹group and said R²¹ group is alkyl (e.g. methyl). In another example ofthis embodiment there are no R²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R¹⁴ are as defined for formula (I) orany of the embodiments thereof.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, R¹⁰, and R²¹ are as defined for formula (I) orany of the embodiments thereof. In one example of this embodiment thereare 0 to 2 R²¹ groups (i.e. there are no R²¹ groups, or there is one R²¹group, or there are two independently selected R²¹ groups) in ring B. Inanother example of this embodiment there are two independently selectedR²¹ groups in ring B. In another example of this embodiment there is oneR²¹ group in ring B. In one example of this embodiment there are 0 to 2R²¹ groups in ring B wherein said R²¹ groups are the same or differentalkyl groups (e.g. methyl). In another example of this embodiment thereare two independently selected R²¹ groups in ring B wherein each R²¹group is the same or different alkyl group (e.g., methyl). In anotherexample of this embodiment there is one R²¹ group and said R²¹ group isalkyl (e.g. methyl). In another example of this embodiment there are noR²¹ groups in ring B.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of:

wherein R⁵, R⁶, R⁷, R⁹, and R¹⁰ are as defined for formula (I) or any ofthe embodiments thereof.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2A.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3A.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4A.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5A.

In another embodiment of this invention the compound of formula (I) is acompound of formula 6A.

In another embodiment of this invention the compound of formula (I) is acompound of formula 7A.

In another embodiment of this invention the compound of formula (I) is acompound of formula 8A.

In another embodiment of this invention the compound of formula (I) is acompound of formula 9A:

wherein in one example the ring B R²¹ group is alkyl, and in anotherexample the ring B R²¹ group is methyl.

In another embodiment of this invention the compound of formula (I) is acompound of formula 9A:

wherein in one example the ring B R²¹ group is alkyl, and in anotherexample the ring B R²¹ group is methyl.

In another embodiment of this invention the compound of formula (I) is acompound of formula 9A:

wherein in one example the ring B R²¹ group is alkyl, and in anotherexample the ring B R²¹ group is methyl.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2E.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3E.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4E.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5E.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2F.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3F.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4F.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5F.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2G.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3G.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4G.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5G.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2H.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3H.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4H.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5H.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2I.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3I.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4I.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5I.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2J.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3J.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4J.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5J.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2K.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3K.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4K.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5K.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2L.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3L.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4L.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5L.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2M.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3M.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4M.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5M.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2N.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3N.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4N.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5N.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2O.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3O.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4O.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5O.

In another embodiment of this invention the compound of formula (I) is acompound of formula 2P.

In another embodiment of this invention the compound of formula (I) is acompound of formula 3P.

In another embodiment of this invention the compound of formula (I) is acompound of formula 4P.

In another embodiment of this invention the compound of formula (I) is acompound of formula 5P.

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, 8D, 2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H,5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M,3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, and 5P (asdefined above including the examples thereof), wherein the —R¹⁰—R⁹moiety is selected from the group consisting of:

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, and 8D (as defined above including the examples thereof),wherein the —R¹⁰—R⁹ moiety is selected from the group consisting of:

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, 8D, 2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H,5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M,3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, and 5P (asdefined above including the examples thereof), wherein the —R¹⁰—R⁹moiety is selected from the group consisting of:

wherein R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g.fluoro substituted phenyl, such as, for example, p-F-phenyl).

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, and 8D (as defined above including the examples thereof),wherein the —R¹⁰—R⁹ moiety is selected from the group consisting of:

wherein R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g.fluoro substituted phenyl, such as, for example, p-F-phenyl).

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, 8D, 2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H,5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M,3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, and 5P (asdefined above including the examples thereof), wherein the —R¹⁰—R⁹moiety is:

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, and 8D (as defined above including the examples thereof),wherein the —R¹⁰—R⁹ moiety is:

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, 8D, 2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H,5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M,3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, and 5P (asdefined above including the examples thereof), wherein the —R¹⁰—R⁹moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A,2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D,6D, 7D, and 8D (as defined above including the examples thereof),wherein the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 2A,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 3A,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 4A,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 5A,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 6A,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 7A,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 8A,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 2B,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 3B,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 4B,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 5B,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 6B,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 7B,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 8B,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 2C,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 3C,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 4C,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 5C,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 6C,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 7C,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 8C,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 2D,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 3D,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 4D,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 5D,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 6D,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 7D,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In one embodiment of this invention the compound of formula (I) is 8D,the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2E, 3E, 4E, 5E, 2F, 3F, 4F,5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K,3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O,5O, 2P, 3P, 4P, and 5P, wherein the —R¹⁰—R⁹ moiety is selected from thegroup consisting of:

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2E, 3E, 4E, 5E, 2F, 3F, 4F,5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K,3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O,5O, 2P, 3P, 4P, and 5P, wherein the —R¹⁰—R⁹ moiety is selected from thegroup consisting of:

wherein R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g.fluoro substituted phenyl, such as, for example, p-F-phenyl).

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2E, 3E, 4E, 5E, 2F, 3F, 4F,5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K,3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O,5O, 2P, 3P, 4P, and 5P, wherein the —R¹⁰—R⁹ moiety is:

In another embodiment of this invention, the compounds of formula (I)are selected from the group consisting of: 2E, 3E, 4E, 5E, 2F, 3F, 4F,5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K,3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O,5O, 2P, 3P, 4P, and 5P, wherein the —R¹⁰—R⁹ moiety is:

R⁶ is alkyl (e.g., methyl), and R⁷ is substituted phenyl (e.g. fluorosubstituted phenyl, such as, for example, p-F-phenyl).

A representative compound of this invention is:

Thus, in the embodiments above directed to compounds 2A, 3A, 4A, 5A, 6A,7A, 8A, 2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D,4D, 5D, 6D, 7D, and 8D,

can have the stereochemistry:

Also, in the embodiments above directed to compounds 2A, 3A, 4A, 5A, 6A,7A, 8A, 2B, 3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, and 8C, theR²¹ groups on ring B can have the stereochemistry:

Also, in the embodiments above directed to compounds 2E, 3E, 4E, 5E, 2F,3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J,5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O,3O, 4O, 5O, 2P, 3P, 4P, and 5P,

can have the stereochemistry:

Also, in the embodiments above directed to compounds 2E, 3E, 4E, 5E, 2F,3F, 4F, 5F, 2G, 3G, 4G, 5G, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K,5K, 2M, 3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, and 5O, the R²¹ groupson ring B can have the stereochemistry:

In another embodiment of this invention R²¹ is selected from the groupconsisting of: alkyl, —OR¹⁶, —C(O)OR¹⁵, —C(O)NR¹⁵R¹⁶, and alkylsubstituted with 1 to 5 independently selected R²² groups (e.g., halo,such as, for example, F, Cl, and Br).

In another embodiment of this invention R²¹ is selected from the groupconsisting of: alkyl, —OR¹⁶, —C(O)OR¹⁵, —C(O)NR¹⁶R¹⁶, and alkylsubstituted with 1 to 5 independently selected R²² groups (e.g., halo,such as, for example, F, Cl, and Br, and wherein in one example thealkyl substituted R²¹ group is —CF₃), wherein R¹⁵ and R¹⁶ areindependently selected from the group consisting of: H, alkyl,(R¹⁸)_(n)-arylalkyl- (wherein, for example, n is 1, and R¹⁸ is —OR²⁰,and R²⁰ is alkyl (e.g., methyl), cycloalkyl (e.g., cyclobutyl), and(R¹⁸)_(n)-alkyl (e.g, n is 1, R¹⁸ is —OR²⁰, and R²⁰ is alkyl (e.g.,methyl).

In another embodiment of this invention R²¹ is selected from the groupconsisting of: (a) alkyl, —OR¹⁵ (wherein R¹⁵ is alkyl, e.g., methyl andethyl), (b) —C(O)OR¹⁵ (wherein R¹⁵ is alkyl,e.g., methyl), (c)—C(O)NR¹⁵R¹⁶ (wherein R¹⁵ and R¹⁶ are independently selected from thegroup consisting of: H, alkyl, (R¹⁸)_(n)-arylalkyl- (wherein, forexample, n is 1, and R¹⁸ is —OR²⁰, and R²⁰ is alkyl (e.g., methyl),cycloalkyl (e.g., cyclobutyl), and (R¹⁸)_(n)-alkyl (e.g, n is 1, R¹⁸ is—OR²⁰, and R²⁰ is alkyl (e.g., methyl), and in one example, only one ofR¹⁵ and R¹⁶ is H), and (d) alkyl substituted with 1 to 5 independentlyselected R²² groups (e.g., halo, such as, for example, F, Cl, and Br,and wherein in one example the alkyl substituted R²¹ group is —CF₃).

Other embodiments of this invention are directed to compounds of formula(I) wherein R^(1A) is selected from the group consisting of:benzofusedcycloalkyl (i.e., fused benzocycloalkyl), fusedbenzoheterocycloalkyl, fused heteroarylcycloalkyl, fusedheteroarylheterocycloalkyl, and wherein said R^(1A) groups areoptionally substituted with 1-5 independently selected R²¹ groups. Inone example, the R²¹ groups are halo (e.g., F).

Examples of the fused ring R⁶ or R⁷ groups include, but are not limitedto:

wherein each Y is independently selected from the group consisting of:—O—, —NR¹⁴— and —C(R²¹)_(q)—, (wherein q is 0, 1 or 2 and each R²¹ isindependently selected), and wherein R¹⁴ and R²¹ are as defined forformula (I). Examples of these fused ring R⁶ or R⁷ groups include, forexample:

Compounds of formula (I) also include compounds wherein R⁶ or R⁷ is analkyl group (e.g., methyl or ethyl) substituted with one R²¹ group.Examples of such groups include alkyl (e.g., methyl or ethyl)substituted with the R²¹ moiety aryl (e.g., phenyl or naphthyl).Examples of said R⁶ or R⁷ groups also include alkyl (e.g., methyl orethyl) substituted with the R²¹ moiety aryl (e.g., phenyl or naphthyl),which in turn is substituted with one or more (e.g., one or two)independently selected R²² groups (e.g., R²² is halo, such as, forexample, F).

Examples of the substituted R⁶ or R⁷ alkyl groups include, but are notlimited to:

Other embodiments of this invention are directed to compounds of formula(I) wherein R⁶ or R⁷ is a cycloalkyl group (e.g., cyclopropyl orcyclobutyl) substituted with one R²¹ group (e.g., aryl, such as, forexample, phenyl), or a cycloalkyl group (e.g., cyclopentyl orcyclohexyl) substituted with one R²¹ group (e.g., aryl, such as, forexample, phenyl) which in turn is substituted with one or more (e.g.,one or two) independently selected R²² groups (e.g., halo, such as, forexample, F). In one example the R²¹ group is bound to the same carbon ofthe R⁶ or R⁷ group that binds the R R⁶ or R⁷ group to the rest of themolecule.

Examples of the cycloalkyl R⁶ or R⁷ groups include, but are not limitedto:

such as, for example,

wherein s is 0 (i.e., the ring is cyclopropyl), or 1 (i.e., the ring iscyclobutyl). Examples of these R⁶ or R⁷ groups include, but are notlimited to:

such as, for example,

wherein s is 0 (i.e., the ring is cyclopropyl), or 1 (i.e., the ring iscyclobutyl).

Other embodiments of this invention are directed to compounds of formula(I) wherein R⁶ or R⁷ is

wherein Z is selected from the group consisting of: (1) —O—, (2) —NR¹⁴—,(3) —C(R²¹)_(q)— wherein q is 0, 1 or 2, and each R²¹ is independentlyselected, (4) —C(R²¹)_(q)—C(R²¹)_(q)— wherein each q is independently 0,1 or 2 and each R²¹ is independently selected, (5)—(C(R²¹)_(q))_(q)—O—(C(R²¹)_(q))_(q)— wherein each q is independently 0,1 or 2, and each R²¹ is independently selected, and (6)—(C(R²¹)_(q))_(q)—N(R¹⁴)—(C(R²¹)_(q))_(q)— wherein each q isindependently 0, 1 or 2, and each R²¹ is independently selected.Examples of R²¹ include, but are not limited to, aryl (e.g., phenyl) andaryl (e.g., phenyl) substituted with one or more (e.g., one or two, orone) independently selected R²² groups (e.g., halo, such as, forexample, F). Examples of this R⁶ or R⁷ include, but are not limited to:

Thus, examples of this R⁶ or R⁷ group include, but are not limited to:

Examples of R⁶ or R⁷ also include, but are not limited to:

Examples of the R⁶ or R⁷ group

also include, but are not limited to:

Examples of the R⁶ or R⁷ group

also include, but are not limited to:

Examples of the R⁶ or R⁷ group

also include, but are not limited to:

Examples of the R⁶ or R⁷ group

also include, but are not limited to:

Other embodiments of this invention are directed to compounds of formula(I) wherein R¹⁰ is aryl (e.g., phenyl) or aryl (e.g., phenyl)substituted with one or more (e.g., one or two, or one) R²¹ groups(e.g., −OR¹⁵, wherein, for example, R¹⁵ is alkyl, such as, for example,methyl), and R⁹ is heteroaryl (e.g., imidazolyl) or heteroaryl (e.g.,imidazolyl) substituted with one or more (e.g., one or two, or one) R²¹groups (e.g., alkyl, such as, for example, methyl).

Thus, examples of the —R¹⁰—R⁹ moiety moiety of the compounds of thisinvention include, but are not limited to:

wherein q is 0, 1 or 2, such as, for example,

such as, for example,

wherein R¹⁵ is alkyl (e.g., methyl), such as, for example,

wherein R¹⁵ is alkyl (e.g., methyl), such as, for example,

wherein R¹⁵ is alkyl (e.g., methyl), such as, for example,

In another embodiment of the compounds of formula (I) R⁶ or R⁷ isbenzofusedcycloalkyl.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is:

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is:

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is:

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is:

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, and said alkyl is

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkyl(e.g., (a), (b) or (c) described above) substituted with one R²¹ groupwherein said R²¹ group is aryl.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkyl(e.g., (a), (b) or (c) described above) substituted with one R²¹ groupwherein said R²¹ group is phenyl.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkyl(e.g., (a), (b) or (c) described above) substituted with one R²¹ groupwherein said R²¹ group is naphthyl.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, and said R²¹ group is substituted withtwo independently selected R²² groups.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, and said R²¹ group is substituted withone R²² group.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said alkyl group is (a) (e.g.,(b) or (c)), as described above, and said R²¹ group is substituted withtwo independently selected R²² groups.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said alkyl group is (a) (e.g.,(b) or (c)), as described above, and said R²¹ group is substituted withone R²² group.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said R²¹ group is aryl, and saidR²¹ group is substituted with two independently selected R²² groups.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said R²¹ group is aryl, saidalkyl group is (a) (e.g., (b) or (c)), as described above, and said R²¹group is substituted with two independently selected R²² groups.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said R²¹ group is aryl, whereinsaid alkyl group is (a) (e.g., (b) or (c)), as described above, and saidR²¹ group is substituted with one R²² group.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said R²¹ group is aryl, saidalkyl group is (a) (e.g., (b) or (c)), as described above, and said R²¹group is substituted with two independently selected R²² groups, andeach R²² is halo.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said R²¹ group is aryl, whereinsaid alkyl group is (a) (e.g., (b) or (c)), as described above, and saidR²¹ group is substituted with one R²² group and said R²² is halo.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said R²¹ group is aryl, saidalkyl group is (a) (e.g., (b) or (c)), as described above, and said R²¹group is substituted with two independently selected R²² groups, andeach R²² is F.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is alkylsubstituted with one R²¹ group, wherein said R²¹ group is aryl, whereinsaid alkyl group is (a) (e.g., (b) or (c)), as described above, and saidR²¹ group is substituted with one R²² group. and said R²² is F.

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is:

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is:

In another embodiment of the compounds of formula (I) R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

In another embodiment of this invention R⁶ or R⁷ is:

Examples of R²¹ groups include —OR¹⁵ wherein, for example, R¹⁵ is alkyl(such as methyl or ethyl), or R¹⁵ is cycloalkylalkyl (such as, forexample, —CH₂-cyclopropyl), or R¹⁵ is -alkyl-(R¹⁸)_(n) (wherein, forexample, said R¹⁸ is —OR²⁰, and said R²⁰ is alkyl, and wherein examplesof said -alkyl-(R¹⁸)_(n) moiety is —(CH₂)₂OCH₃).

Examples of the R²¹ moiety in the embodiments of this invention include,but are not limited to: (a) —OR¹⁵, (b) —OR¹⁵ wherein R¹⁵ is alkyl, (c)—OR¹⁵ wherein R¹⁵ is alkyl and said alkyl is methyl or ethyl, (d) —OR¹⁵wherein R¹⁵ is cycloalkylalkyl, (e) —OR¹⁵ wherein R¹⁵ is-alkyl-(R¹⁸)_(n), (f) —OR¹⁵ wherein R¹⁵ is -alkyl-(R¹⁸)_(n) and whereinsaid R¹⁸ is —OR²⁰, (g) —OR¹⁵ wherein R¹⁵ is -alkyl-(R¹⁸)_(n) and whereinsaid R¹⁸ is —OR²⁰ and said R²⁰ is alkyl. Examples of the R²¹ moietyinclude but are not limited to: —OCH₃, —OCH₂CH₃, —O(CH₂)₂OCH₃, and—CH₂-cyclopropyl.

Examples of R²¹ also include —C(O)OR¹⁵ wherein, for example, R¹⁵ isalkyl, such as, for example, methyl).

Examples of R²¹ also include —C(O)NR¹⁵R¹⁶, wherein, for example, one ofR¹⁵ or R¹⁶ is H, and the other is selected from the group consisting of:(R¹⁸)_(n)-arylalkyl-, (R¹⁸)_(n)-alkyl-, and cycloalkyl. In one exampleof this —C(O)NR¹⁵R¹⁶ moiety the R¹⁸ is —OR²⁰, n is 1, R²⁰ is alkyl, saidcycloalkyl is cyclobutyl, and said arylalkyl- is benzyl.

Examples of R²¹ also include halo (e.g., Br, Cl or F).

Examples of R²¹ also include arylalkyl, such as, for example, benzyl.

In the embodiments below, Groups A, B and C are defined as follows:

-   -   (1) Group A: 2A, 3A, 4A, 5A, 6A, 7A, 8A, 2B, 3B, 4B, 5B, 6B, 7B,        8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D, 6D, 7D, 8D, 2E,        3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H, 2I,        3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M,        3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, 5P and        Compounds 9, and 15 to 26;    -   (2) Group B: 2A, 3A, 4A, 5A, 6A, 7A, 8A, 2B, 3B, 4B, 5B, 6B, 7B,        8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D, 6D, 7D, 8D, and        Compounds 9, and 15 to 26; and    -   (3) Group C: 2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H,        3H, 4H, 5H, 2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L,        3L, 4LH, 5L, 2M, 3M, 4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P,        3P, 4P, and 5P.

One embodiment of this invention is directed to a compound of formula(I).

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of a compound of formula (I). And in one example thesalt is a salt of a compound selected from the group consisting of GroupA. And in another example the salt is a salt of a compound selected fromthe group consisting of Group B. And in another example the salt is asalt of a compound selected from the group consisting of Group C. And inanother example the salt is a salt of a compound selected from the groupconsisting of Group B. And in another example the salt is a salt of acompound selected from the group consisting of compounds 9, and 15 to26.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of a compound of formula (I). And in one example theester is an ester of a compound selected from the group consisting ofGroup A. And in another example the ester is an ester of a compoundselected from the group consisting of Group B. And in another examplethe ester is an ester of a compound selected from the group consistingof Group C. And in another example the ester is an ester of a compoundselected from the group consisting of Group B. And in another examplethe ester is an ester of a compound selected from the group consistingof compounds 9, and 15 to 26.

Another embodiment of this invention is directed to a solvate of acompound of formula (I). And in one example the solvate is a solvate ofa compound selected from the group consisting of Group A. And in anotherexample the solvate is a solvate of a compound selected from the groupconsisting of Group B. And in another example the solvate is a solvateof a compound selected from the group consisting of Group C. And inanother example the solvate is a solvate of a compound selected from thegroup consisting of Group B. And in another example the solvate is asolvate of a compound selected from the group consisting of compounds 9,and 15 to 26.

Another embodiment of this invention is directed to a compound offormula (I) in pure and isolated form. And in one example the compoundof formula (I) is selected from the group consisting of compounds 9, and15 to 26.

Another embodiment of this invention is directed to a compound offormula (I) in pure form. And in one example the compound of formula (I)is selected from the group consisting of compounds 9, and 15 to 26.

Another embodiment of this invention is directed to a compound offormula (I) in isolated form. And in one example the compound of formula(I) is selected from the group consisting of compounds 9, and 15 to 26.

Another embodiment of this invention is directed to a compound offormula (I) selected from the group consisting of compounds 9, and 15 to26.

Another embodiment of this invention is directed to pharmaceuticallyacceptable salt of a compound of formula (I), said compound beingselected from the group consisting of compounds 9, and 15 to 26.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 9.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 15.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 16.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 17.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 18.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 20.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 21.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 22.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 23.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 24.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 25.

Another embodiment of this invention is directed to a compound offormula (I) wherein said compound is compound 26.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 9.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 15.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 16.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 17.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 18.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 20.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 21.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 22.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 23.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 24.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 25.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 26.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 9.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 15.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 16.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 17.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 18.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 20.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable salt of compound 21.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 22.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 23.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 24.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 25.

Another embodiment of this invention is directed to a pharmaceuticallyacceptable ester of compound 26.

Another embodiment of this invention is directed to a solvate ofcompound 9.

Another embodiment of this invention is directed to a solvate ofcompound 15.

Another embodiment of this invention is directed to a solvate ofcompound 16.

Another embodiment of this invention is directed to a solvate ofcompound 17.

Another embodiment of this invention is directed to a solvate ofcompound 18.

Another embodiment of this invention is directed to a solvate ofcompound 20.

Another embodiment of this invention is directed to a solvate ofcompound 21.

Another embodiment of this invention is directed to a solvate ofcompound 22.

Another embodiment of this invention is directed to a solvate ofcompound 23.

Another embodiment of this invention is directed to a solvate ofcompound 24.

Another embodiment of this invention is directed to a solvate ofcompound 25.

Another embodiment of this invention is directed to a solvate ofcompound 26.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising a therapeutically effective amount of at leastone compound of Formula (I), or a pharmaceutically acceptable salt,solvate, or ester thereof, and at least one pharmaceutically acceptablecarrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula (I) and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of a pharmaceuticallyacceptable salt of one or more (e.g., one) compounds of formula (I) anda pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of a pharmaceuticallyacceptable ester of one or more (e.g., one) compounds of formula (I) anda pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of a solvate of one or more(e.g., one) compounds of formula (I) and a pharmaceutically acceptablecarrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula (I), and an effective amount of one or more (e.g.,one) other pharmaceutically active ingredients (e.g., drugs), and apharmaceutically acceptable carrier. Examples of the otherpharmaceutically active ingredients include, but are not limited todrugs selected form the group consisting of: (a) drugs useful for thetreatment of Alzheimer's disease, (b) drugs useful for inhibiting thedeposition of amyloid protein (e.g., amyloid beta protein) in, on oraround neurological tissue (e.g., the brain), (c) drugs useful fortreating neurodegenerative diseases, and (d) drugs useful for inhibitinggamma-secretase.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising a therapeutically effective amount of at leastone compound of Formula (I), or a pharmaceutically acceptable salt,solvate, or ester thereof, and at least one pharmaceutically acceptablecarrier, and a therapeutically effective amount of one or more compoundsselected from the group consisting of cholinesterase inhibitors, Aβantibody inhibitors, gamma secretase inhibitors and beta secretaseinhibitors.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula (I), and effective amount of one or more BACEinhibitors, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula (I), and effective amount of one or morecholinesterase inhibitors (e.g., acetyl- and/or butyrylchlolinesteraseinhibitors), and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula (I), and effective amount of one or more muscarinicantagonists (e.g., m₁ or m₂ antagonists), and a pharmaceuticallyacceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of Exelon (rivastigmine),and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of Cognex (tacrine), and apharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of a Tau kinase inhibitor,and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more Tau kinaseinhibitor (e.g., GSK3beta inhibitor, cdk5 inhibitor, ERK inhibitor), anda pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one anti-Abeta vaccine(active immunization), and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more APP ligands,and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more agents thatupregulate insulin degrading enzyme and/or neprilysin, and apharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more cholesterollowering agents (for example, statins such as Atorvastatin, Fluvastatin,Lovastatin, Mevastatin, Pitavastatin, Pravastatin, Rosuvastatin,Simvastatin, and cholesterol absorption inhibitor such as Ezetimibe),and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more fibrates(for example, clofibrate, Clofibride, Etofibrate, Aluminium Clofibrate),and a pharmaceutically acceptable carrier

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more LXRagonists, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more LRP mimics,and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more 5-HT6receptor antagonists, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more nicotinicreceptor agonists, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more H3 receptorantagonists, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more histonedeacetylase inhibitors, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more hsp90inhibitors, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more m1muscarinic receptor agonists, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to combinations, i.e.,a pharmaceutical composition, comprising a pharmaceutically acceptablecarrier, an effective (i.e., therapeutically effective) amount of one ormore compounds of formula (I), in combination with an effective (i.e.,therapeutically effective) amount of one or more compounds selected fromthe group consisting of cholinesterase inhibitors (such as, for example,(±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-onehydrochloride, i.e., donepezil hydrochloride, available as the Aricept®brand of donepezil hydrochloride), Aβ antibody inhibitors, gammasecretase inhibitors and beta secretase inhibitors.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more 5-HT6receptor antagonists mGluR1 or mGluR5 positive allosteric modulators oragonists, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more one mGluR2/3antagonists, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or moreanti-inflammatory agents that can reduce neuroinflammation, and apharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or moreProstaglandin EP2 receptor antagonists, and a pharmaceuticallyacceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more PAI-1inhibitors, and a pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a pharmaceuticalcomposition comprising an effective amount of one or more (e.g., one)compounds of formula I, and effective amount of one or more agents thatcan induce Abeta efflux such as gelsolin, and a pharmaceuticallyacceptable carrier.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to pharmaceutical compositions wherein the compoundof formula (I) is selected from the group consisting of Group A.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to pharmaceutical compositions wherein the compoundof formula (I) is selected from the group consisting of Group B.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to pharmaceutical compositions wherein the compoundof formula (I) is selected from the group consisting of Group C.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to pharmaceutical compositions wherein the compoundof formula (I) is selected from the group consisting of compounds 9, and15 to 25.

The compounds of formula (I) can be useful as gamma secretase modulatorsand can be useful in the treatment and prevention of diseases such as,for example, central nervous system disorders (such as Alzheimersdisease and Downs Syndrome), mild cognitive impairment, glaucoma,cerebral amyloid angiopathy, stroke, dementia, microgliosis, braininflammation, and olfactory function loss.

Another embodiment of this invention is directed to a method of treatinga central nervous system disorder comprising administering atherapeutically effective amount of at least one compound of Formula (I)to a patient in need of such treatment.

Another embodiment of this invention is directed to a method of treatinga central nervous system disorder comprising administering atherapeutically effective amount of a pharmaceutical compositioncomprising a therapeutically effective amount of at least one compoundof Formula (I), or a pharmaceutically acceptable salt, solvate, or esterthereof, and at least one pharmaceutically acceptable carrier.

Another embodiment of this invention is directed to a method of treatinga central nervous system disorder comprising administering atherapeutically effective amount of a pharmaceutical compositioncomprising a therapeutically effective amount of at least one compoundof Formula (I), or a pharmaceutically acceptable salt, solvate, or esterthereof, and at least one pharmaceutically acceptable carrier, and atherapeutically effective amount of one or more compounds selected fromthe group consisting of cholinesterase inhibitors, Aβ antibodyinhibitors, gamma secretase inhibitors and beta secretase inhibitors.

Another embodiment of this invention is directed to a method formodulating (including inhibiting, antagonizing and the like)gamma-secretase comprising administering an effective amount of one ormore (e.g., one) compounds of formula (I) to a patient in need of suchtreatment.

Another embodiment of this invention is directed to a method formodulating (including inhibiting, antagonizing and the like)gamma-secretase, comprising administering an effective amount of acompound of formula (I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingone or more neurodegenerative diseases, comprising administering aneffective amount of one or more (e.g., one) compounds of formula (I) toa patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingone or more neurodegenerative diseases, comprising administering aneffective amount of a compound of formula (I) to a patient in need oftreatment.

Another embodiment of this invention is directed to a method ofinhibiting the deposition of amyloid protein (e.g., amyloid betaprotein) in, on or around neurological tissue (e.g., the brain),comprising administering an effective amount of one or more (e.g., one)compounds of formula (I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method ofinhibiting the deposition of amyloid protein (e.g., amyloid betaprotein) in, on or around neurological tissue (e.g., the brain),comprising administering an effective amount of a compound of formula(I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more (e.g., one) compounds of formula (I) to a patient in need oftreatment.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of acompound of formula (I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingmild cognitive impairment, glaucoma, cerebral amyloid angiopathy,stroke, dementia, microgliosis, brain inflammation, or olfactoryfunction loss, comprising administering an effective (i.e.,therapeutically effective) amount of one or more (e.g., one) compoundsof formula (I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingmild cognitive impairment, glaucoma, cerebral amyloid angiopathy,stroke, dementia, microgliosis, brain inflammation, or olfactoryfunction loss, comprising administering an effective (i.e.,therapeutically effective) amount of a compound of formula (I) to apatient in need of treatment.

Another embodiment of this invention is directed to a method of treatingmild cognitive impairment, comprising administering an effective amountof one or more (e.g., one) compounds of formula (I) to a patient in needof treatment.

Another embodiment of this invention is directed to a method of treatingglaucoma, comprising administering an effective amount of one or more(e.g., one) compounds of formula (I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingcerebral amyloid angiopathy, comprising administering an effectiveamount of one or more (e.g., one) compounds of formula (I) to a patientin need of treatment.

Another embodiment of this invention is directed to a method of treatingstroke, comprising administering an effective amount of one or more(e.g., one) compounds of formula (I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingdementia, comprising administering an effective amount of one or more(e.g., one) compounds of formula (I) to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingmicrogliosis, comprising administering an effective amount of one ormore (e.g., one) compounds of formula (I) to a patient in need oftreatment.

Another embodiment of this invention is directed to a method of treatingbrain inflammation, comprising administering an effective amount of oneor more (e.g., one) compounds of formula (I) to a patient in need oftreatment.

Another embodiment of this invention is directed to a method of treatingolfactory function loss, comprising administering an effective amount ofone or more (e.g., one) compounds of formula (I) to a patient in need oftreatment.

Another embodiment of this invention is directed to a method of treatingDowns syndrome, comprising administering an effective amount of one ormore (e.g., one) compounds of formula (I) to a patient in need oftreatment.

Another embodiment of this invention is directed to a method of treatingDowns syndrome, comprising administering an effective amount of acompound of formula (I) to a patient in need of treatment.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to methods of treating wherein the compound offormula (I) is selected from the group consisting of Group A.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to methods of treating wherein the compound offormula (I) is selected from the group consisting of Group B.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to methods of treating wherein the compound offormula (I) is selected from the group consisting of Group C.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to methods of treating wherein the compound offormula (I) is selected from the group consisting of compounds 9, and 15to 25.

This invention also provides combination therapies for (1) modulatinggamma-secretase, or (2) treating one or more neurodegenerative diseases,or (3) inhibiting the deposition of amyloid protein (e.g., amyloid betaprotein) in, on or around neurological tissue (e.g., the brain), or (4)treating Alzheimer's disease. The combination therapies are directed tomethods comprising the administration of an effective amount of one ormore (e.g. one) compounds of formula (I) and the administration of aneffective amount of one or more (e.g., one) other pharmaceutical activeingredients (e.g., drugs). The compounds of formula (I) and the otherdrugs can be administered separately (i.e., each is in its own separatedosage form), or the compounds of formula (I) can be combined with theother drugs in the same dosage form.

Thus, other embodiments of this invention are directed to any one of themethods of treatment, or methods of inhibiting, described herein,wherein an effective amount of the compound of formula (I) is used incombination with an effective amount of one or more otherpharmaceutically active ingredients (e.g., drugs). The otherpharmaceutically active ingredients (i.e., drugs) are selected from thegroup consisting of: BACE inhibitors (beta secretase inhibitors);muscarinic antagonists (e.g., m₁ agonists or m₂ antagonists);cholinesterase inhibitors (e.g., acetyl- and/or butyrylchlolinesteraseinhibitors); gamma secretase inhibitors; gamma secretase modulators;HMG-CoA reductase inhibitors; non-steroidal anti-inflammatory agents;N-methyl-D-aspartate receptor antagonists; anti-amyloid antibodies;vitamin E; nicotinic acetylcholine receptor agonists; CB1 receptorinverse agonists or CB1 receptor antagonists; an antibiotic; growthhormone secretagogues; histamine H3 antagonists; AMPA agonists; PDE4inhibitors; GABA_(A) inverse agonists; inhibitors of amyloidaggregation; glycogen synthase kinase beta inhibitors; promoters ofalpha secretase activity; PDE-10 inhibitors; Exelon (rivastigmine);Cognex (tacrine); Tau kinase inhibitors (e.g., GSK3beta inhibitors, cdk5inhibitors, or ERK inhibitors); anti-Abeta vaccine; APP ligands; agentsthat upregulate insulin cholesterol lowering agents (for example,statins such as Atorvastatin, Fluvastatin, Lovastatin, Mevastatin,Pitavastatin, Pravastatin, Rosuvastatin, Simvastatin); cholesterolabsorption inhibitors (such as Ezetimibe); fibrates (such as, forexample, for example, clofibrate, Clofibride, Etofibrate, and AluminiumClofibrate); LXR agonists; LRP mimics; nicotinic receptor agonists; H3receptor antagonists; histone deacetylase inhibitors; hsp90 inhibitors;ml muscarinic receptor agonists; 5-HT6 receptor antagonists; mGluR1;mGluR5; positive allosteric modulators or agonists; mGluR2/3antagonists; anti-inflammatory agents that can reduce neuroinflammation;Prostaglandin EP2 receptor antagonists; PAI-1 inhibitors; and agentsthat can induce Abeta efflux such as gelsolin.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more (e.g., one) compounds of formula (I), in combination with aneffective (i.e., therapeutically effective) amount of one or morecholinesterase inhibitors (such as, for example,(±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-onehydrochloride, i.e., donepezil hydrochloride, available as the Aricept®brand of donepezil hydrochloride), to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of acompound of formula (I), in combination with an effective amount of oneor more (e.g., one) cholinesterase inhibitors (such as, for example,(±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-onehydrochloride, i.e., donepezil hydrochloride, available as the Aricept®brand of donepezil hydrochloride), to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more (e.g., one) compounds of formula (I), in combination with aneffective amount of one or more compounds selected from the groupconsisting of Aβ antibody inhibitors, gamma secretase inhibitors andbeta secretase inhibitors.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more (e.g., one) compounds of formula (I), in combination with aneffective amount of one or more BACE inhibitors.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof Exelon (rivastigmine).

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof Cognex (tacrine).

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof a Tau kinase inhibitor.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more Tau kinase inhibitor (e.g., GSK3beta inhibitor, cdk5inhibitor, ERK inhibitor).

This invention also provides a method of treating Alzheimer's disease,comprising administering an effective amount of one or more compounds offormula I, in combination with an effective amount of one anti-Abetavaccination (active immunization).

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more APP ligands.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more agents that upregulate insulin degrading enzyme and/orneprilysin.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more cholesterol lowering agents (for example, statins such asAtorvastatin, Fluvastatin, Lovastatin, Mevastatin, Pitavastatin,Pravastatin, Rosuvastatin, Simvastatin, and cholesterol absorptioninhibitor such as Ezetimibe).

This invention also provides a method of treating Alzheimer's disease,comprising administering an effective amount of one or more compounds offormula I, in combination with an effective amount of one or morefibrates (for example, clofibrate, Clofibride, Etofibrate, AluminiumClofibrate).

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more LXR agonists.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more LRP mimics.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more 5-HT6 receptor antagonists.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more nicotinic receptor agonists.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more H3 receptor antagonists.

This invention also provides a method of treating Alzheimer's disease,comprising administering an effective amount of one or more compounds offormula I, in combination with an effective amount of one or morehistone deacetylase inhibitors.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more hsp90 inhibitors.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more ml muscarinic receptor agonists.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more 5-HT6 receptor antagonists mGluR1 or mGluR5 positiveallosteric modulators or agonists

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more mGluR2/3 antagonists.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more anti-inflammatory agents that can reduceneuroinflammation.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more Prostaglandin EP2 receptor antagonists.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more PAI-1 inhibitors.

Another embodiment of this invention is directed to a method of treatingAlzheimer's disease, comprising administering an effective amount of oneor more compounds of formula I, in combination with an effective amountof one or more agents that can induce Abeta efflux such as gelsolin.

Another embodiment of this invention is directed to a method of treatingDowns syndrome, comprising administering an effective amount of one ormore (e.g., one) compounds of formula (I), in combination with aneffective amount of one or more cholinesterase inhibitors (such as, forexample,(±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-onehydrochloride, i.e., donepezil hydrochloride, available as the Aricept®brand of donepezil hydrochloride), to a patient in need of treatment.

Another embodiment of this invention is directed to a method of treatingDowns syndrome, comprising administering an effective amount of acompound of formula (I), in combination with an effective amount of oneor more (e.g., one) cholinesterase inhibitors (such as, for example,(±)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-onehydrochloride, i.e., donepezil hydrochloride, available as the Aricept®brand of donepezil hydrochloride), to a patient in need of treatment.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to combination therapies (i.e., the above methodsof treating wherein compounds of formula (I) are used in combinationwith other pharmaceutically active ingredients, i.e., drugs) wherein thecompound of formula (I) is selected from the group consisting of GroupA.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to combination therapies (i.e., the above methodsof treating wherein compounds of formula (I) are used in combinationwith other pharmaceutically active ingredients, i.e., drugs) wherein thecompound of formula (I) is selected from the group consisting of GroupB.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to combination therapies (i.e., the above methodsof treating wherein compounds of formula (I) are used in combinationwith other pharmaceutically active ingredients, i.e., drugs) wherein thecompound of formula (I) is selected from the group consisting of GroupC.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to combination therapies (i.e., the above methodsof treating wherein compounds of formula (I) are used in combinationwith other pharmaceutically active ingredients, i.e., drugs) wherein thecompound of formula (I) is selected from the group consisting ofcompounds 9, and 15 to 25.

This invention also provides a kit comprising, in separate containers,in a single package, pharmaceutical compositions for use in combination,wherein one container comprises an effective amount of a compound offormula (I) in a pharmaceutically acceptable carrier, and anothercontainer (i.e., a second container) comprises an effective amount ofanother pharmaceutically active ingredient (as described above), thecombined quantities of the compound of formula (I) and the otherpharmaceutically active ingredient being effective to: (a) treatAlzheimer's disease, or (b) inhibit the deposition of amyloid protein(e.g., amyloid beta protein) in, on or around neurological tissue (e.g.,the brain), or (c) treat neurodegenerative diseases, or (d) modulate theactivity of gamma-secretase, or (e) mild cognitive impairment, or (f)glaucoma, or (g) cerebral amyloid angiopathy, or (h) stroke, or (i)dementia, or (j) microgliosis, or (k) brain inflammation, or (l)olfactory function loss.

This invention also provides a kit comprising, in separate containers,in a single package, pharmaceutical compositions for use in combination,wherein one container comprises an effective amount of a compound offormula (I) in a pharmaceutically acceptable carrier, and anothercontainer (i.e., a second container) comprises an effective amount ofanother pharmaceutically active ingredient (as described above), thecombined quantities of the compound of formula (I) and the otherpharmaceutically active ingredient being effective to: (a) treatAlzheimer's disease, or (b) inhibit the deposition of amyloid protein(e.g., amyloid beta protein) in, on or around neurological tissue (e.g.,the brain), or (c) treat neurodegenerative diseases, or (d) modulate theactivity of gamma-secretase.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to kits wherein the compound of formula (I) isselected from the group consisting of Group A.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to kits wherein the compound of formula (I) isselected from the group consisting of Group B.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to kits wherein the compound of formula (I) isselected from the group consisting of Group C.

Other embodiments of this invention are directed to any one of the aboveembodiments directed to kits wherein the compound of formula (I) isselected from the group consisting of compounds 9, and 15 to 26.

Examples of cholinesterase inhibitors are tacrine, donepezil,rivastigmine, galantamine, pyridostigmine and neostigmine, with tacrine,donepezil, rivastigmine and galantamine being preferred.

Examples of m₁ agonists are known in the art. Examples of m₂ antagonistsare also known in the art; in particular, m₂ antagonists are disclosedin U.S. Pat. Nos. 5,883,096; 6,037,352; 5,889,006; 6,043,255; 5,952,349;5,935,958; 6,066,636; 5,977,138; 6,294,554; 6,043,255; and 6,458,812;and in WO 03/031412, all of which are incorporated herein by reference.

Examples of BACE inhibitors include those described in: US2005/0119227published Jun. 2, 2005 (see also WO2005/016876 published Feb. 24, 2005),US2005/0043290 published Feb. 24, 2005 (see also WO2005/014540 publishedFeb. 17, 2005), WO2005/058311 published Jun. 30, 2005 (see alsoUS2007/0072852 published Mar. 29, 2007), US2006/0111370 published May25, 2006 (see also WO2006/065277 published Jun. 22, 2006), U.S.application Ser. No. 11/710,582 filed Feb. 23, 2007, US2006/0040994published Feb. 23, 2006 (see also WO2006/014762 published Feb. 9, 2006),WO2006/014944 published Feb. 9, 2006 (see also US2006/0040948 publishedFeb. 23, 2006), WO2006/138266 published Dec. 28, 2006 (see alsoUS2007/0010667 published Jan. 11, 2007), WO2006/138265 published Dec.28, 2006, WO2006/138230 published Dec. 28, 2006, WO2006/138195 publishedDec. 28, 2006 (see also US2006/0281729 published Dec. 14, 2006),WO2006/138264 published Dec. 28, 2006 (see also US2007/0060575 publishedMar. 15, 2007), WO2006/138192 published Dec. 28, 2006 (see alsoUS2006/0281730 published Dec. 14, 2006), WO2006/138217 published Dec.28, 2006 (see also US2006/0287294 published Dec. 21, 2006),US2007/0099898 published May 3, 200 (see also WO2007/050721 publishedMay 3, 2007), WO2007/053506 published May 10, 2007 (see alsoUS2007/099875 published May 3, 2007), U.S. application Ser. No.11/759,336 filed Jun. 7, 2007, U.S. Application Ser. No. 60/874,362filed Dec. 12, 2006, and U.S. Application Ser. No. 60/874,419 filed Dec.12, 2006, the disclosures of each being incorporated incorporated hereinby reference thereto.

It is noted that the carbons of formula (I) and other formulas hereinmay be replaced with 1 to 3 silicon atoms so long as all valencyrequirements are satisfied.

As used above, and throughout this disclosure, the following terms,unless otherwise indicated, shall be understood to have the followingmeanings:

“Patient” includes both human and animals.

“Mammal” means humans and other mammalian animals.

“One or more” means that there is at least one and there can be morethan one, and examples include 1, 2 or 3, or 1 and 2, or 1.

“At least one” means there is at least one and there can be more thanone, and examples include 1, 2 or 3, or 1 and 2, or 1.

“An effective amount” as used to describe the amount of a compound offormula (I) in a pharmaceutical composition, or to describe the amountof a compound of formula (I) used in a method of treatment, or todescribe the amount of a pharmaceutical composition used in a method oftreatment, or to describe the amount of other pharmaceutic ingredients(i.e., drugs) used in a pharmaceutical compositions or methods oftreatment, means a therapeutically effective amount.

“Bn” means benzyl.

“Et” means ethyl.

“i-pr” means isopropyl.

“Me” means methyl.

“Pr” means propyl.

“t-Bu” means tert-butyl.

“TBDMSCl” means tert-butyldimethylsilyl chloride.

“DMAP” means 4-(dimethylamino)pyridine.

“Carbocyclic” means a non-aromatic saturated or unsaturated mono- ormulticyclic ring system comprising about 3 to about 10 carbon atoms,preferably about 5 to about 10 carbon atoms. Carbocyclic rings includecycloalkyl rings and cycloalkenyl rings as defined below. Thus, examplesof carbocyclic rings include bicyclic rings, such as, for example,norbornyl, adamantly, norbornenyl, and

The carbocyclic rings are optionally substituted with one or moreindependently selected “ring system substituents” as defined below.

“Fused benzocycloalkyl ring” means a phenyl ring fused to a cycloalkylring (as cycloalkyl is defined below), such as, for example,

“Alkyl” means an aliphatic hydrocarbon group which may be straight orbranched and comprising about 1 to about 20 carbon atoms in the chain.Preferred alkyl groups contain about 1 to about 12 carbon atoms in thechain. More preferred alkyl groups contain about 1 to about 6 carbonatoms in the chain. Branched means that one or more lower alkyl groupssuch as methyl, ethyl or propyl, are attached to a linear alkyl chain.“Lower alkyl” means a group having about 1 to about 6 carbon atoms inthe chain which may be straight or branched. “Alkyl” may beunsubstituted or optionally substituted by one or more substituentswhich may be the same or different, each substituent being independentlyselected from the group consisting of halo, alkyl, aryl, cycloalkyl,cyano, hydroxy, alkoxy, alkylthio, amino, oxime (e.g., ═N—OH),—NH(alkyl), —NH(cycloalkyl), —N(alkyl)₂, —O—C(O)-aryl,—O—C(O)-cycloalkyl, carboxy and —C(O)O-alkyl. Non-limiting examples ofsuitable alkyl groups include methyl, ethyl, n-propyl, isopropyl andt-butyl.

“Alkenyl” means an aliphatic hydrocarbon group containing at least onecarbon-carbon double bond and which may be straight or branched andcomprising about 2 to about 15 carbon atoms in the chain. Preferredalkenyl groups have about 2 to about 12 carbon atoms in the chain; andmore preferably about 2 to about 6 carbon atoms in the chain. Branchedmeans that one or more lower alkyl groups such as methyl, ethyl orpropyl, are attached to a linear alkenyl chain. “Lower alkenyl” meansabout 2 to about 6 carbon atoms in the chain which may be straight orbranched. “Alkenyl” may be unsubstituted or optionally substituted byone or more substituents which may be the same or different, eachsubstituent being independently selected from the group consisting ofhalo, alkyl. aryl, cycloalkyl, cyano, alkoxy and —S(alkyl). Non-limitingexamples of suitable alkenyl groups include ethenyl, propenyl,n-butenyl, 3-methylbut-2-enyl, n-pentenyl, octenyl and decenyl.

“Alkylene” means a difunctional group obtained by removal of a hydrogenatom from an alkyl group that is defined above. Non-limiting examples ofalkylene include methylene, ethylene and propylene.

“Alkynyl” means an aliphatic hydrocarbon group containing at least onecarbon-carbon triple bond and which may be straight or branched andcomprising about 2 to about 15 carbon atoms in the chain. Preferredalkynyl groups have about 2 to about 12 carbon atoms in the chain; andmore preferably about 2 to about 4 carbon atoms in the chain. Branchedmeans that one or more lower alkyl groups such as methyl, ethyl orpropyl, are attached to a linear alkynyl chain. “Lower alkynyl” meansabout 2 to about 6 carbon atoms in the chain which may be straight orbranched. Non-limiting examples of suitable alkynyl groups includeethynyl, propynyl, 2-butynyl and 3-methylbutynyl. “Alkynyl” may beunsubstituted or optionally substituted by one or more substituentswhich may be the same or different, each substituent being independentlyselected from the group consisting of alkyl, aryl and cycloalkyl.

“Aryl” means an aromatic monocyclic or multicyclic ring systemcomprising about 6 to about 14 carbon atoms, preferably about 6 to about10 carbon atoms. The aryl group can be optionally substituted with oneor more “ring system substituents” which may be the same or different,and are as defined herein. Non-limiting examples of suitable aryl groupsinclude phenyl and naphthyl.

“Heteroaryl” means an aromatic monocyclic or multicyclic ring systemcomprising about 5 to about 14 ring atoms, preferably about 5 to about10 ring atoms, in which one or more of the ring atoms is an elementother than carbon, for example nitrogen, oxygen or sulfur, alone or incombination. Preferred heteroaryls contain about 5 to about 6 ringatoms. The “heteroaryl” can be optionally substituted by one or more“ring system substituents” which may be the same or different, and areas defined herein. The prefix aza, oxa or thia before the heteroarylroot name means that at least a nitrogen, oxygen or sulfur atomrespectively, is present as a ring atom. A nitrogen atom of a heteroarylcan be optionally oxidized to the corresponding N-oxide. “Heteroaryl”may also include a heteroaryl as defined above fused to an aryl asdefined above. Non-limiting examples of suitable heteroaryls includepyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridone (includingN-substituted pyridones), isoxazolyl, isothiazolyl, oxazolyl, thiazolyl,pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl,1,2,4-thiadiazolyl, pyrazinyl, pyridazinyl, quinoxalinyl, phthalazinyl,oxindolyl, imidazo[1,2-a]pyridinyl, imidazo[2,1-b]thiazolyl,benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl,quinolinyl, imidazolyl, thienopyridyl, quinazolinyl, thienopyrimidyl,pyrrolopyridyl, imidazopyridyl, isoquinolinyl, benzoazaindolyl,1,2,4-triazinyl, benzothiazolyl and the like. The term “heteroaryl” alsorefers to partially saturated heteroaryl moieties such as, for example,tetrahydroisoquinolyl, tetrahydroquinolyl and the like.

“Aralkyl” or “arylalkyl” means an aryl-alkyl-group in which the aryl andalkyl are as previously described. Preferred aralkyls comprise a loweralkyl group. Non-limiting examples of suitable aralkyl groups includebenzyl, 2-phenethyl and naphthalenylmethyl. The bond to the parentmoiety is through the alkyl.

“Alkylaryl” means an alkyl-aryl-group in which the alkyl and aryl are aspreviously described. Preferred alkylaryls comprise a lower alkyl group.Non-limiting example of a suitable alkylaryl group is tolyl. The bond tothe parent moiety is through the aryl.

“Cycloalkyl” means a non-aromatic mono- or multicyclic ring systemcomprising about 3 to about 10 carbon atoms, preferably about 5 to about10 carbon atoms. Preferred cycloalkyl rings contain about 5 to about 7ring atoms. The cycloalkyl can be optionally substituted with one ormore “ring system substituents” which may be the same or different, andare as defined above. Non-limiting examples of suitable monocycliccycloalkyls include cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyland the like. Non-limiting examples of suitable multicyclic cycloalkylsinclude 1-decalinyl, norbornyl, adamantyl and the like.

“Cycloalkylalkyl” means a cycloalkyl moiety as defined above linked viaan alkyl moiety (defined above) to a parent core. Non-limiting examplesof suitable cycloalkylalkyls include cyclohexylmethyl, adamantylmethyland the like.

“Cycloalkenyl” means a non-aromatic mono or multicyclic ring systemcomprising about 3 to about 10 carbon atoms, preferably about 5 to about10 carbon atoms which contains at least one carbon-carbon double bond.Preferred cycloalkenyl rings contain about 5 to about 7 ring atoms. Thecycloalkenyl can be optionally substituted with one or more “ring systemsubstituents” which may be the same or different, and are as definedabove. Non-limiting examples of suitable monocyclic cycloalkenylsinclude cyclopentenyl, cyclohexenyl, cyclohepta-1,3-dienyl, and thelike. Non-limiting example of a suitable multicyclic cycloalkenyl isnorbornylenyl.

“Cycloalkenylalkyl” means a cycloalkenyl moiety as defined above linkedvia an alkyl moiety (defined above) to a parent core. Non-limitingexamples of suitable cycloalkenylalkyls include cyclopentenylmethyl,cyclohexenylmethyl and the like.

“Halogen” means fluorine, chlorine, bromine, or iodine. Preferred arefluorine, chlorine and bromine. “Halo” refers to fluoro, chloro, bromoor iodo.

“Ring system substituent” means a substituent attached to an aromatic ornon-aromatic ring system which, for example, replaces an availablehydrogen on the ring system. Ring system substituents may be the same ordifferent, each being independently selected from the group consistingof alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, alkylaryl,heteroaralkyl, heteroarylalkenyl, heteroarylalkynyl, alkylheteroaryl,hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, acyl, aroyl, halo,nitro, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl,aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl,alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio,cycloalkyl, heterocyclyl, ═O, ═N—OY₁, —O—C(O)-alkyl, —O—C(O)-aryl,—O—C(O)-cycloalkyl, —C(═N—CN)—NH₂, —C(═NH)—NH₂, —C(═NH)—NH(alkyl), oxime(e.g., ═N—OH), Y₁Y₂N—, Y₁Y₂NC(O)—, Y₁Y₂NSO₂— and —SO₂NY₁Y₂, wherein Y₁and Y₂ can be the same or different and are independently selected fromthe group consisting of hydrogen, alkyl, aryl, cycloalkyl, and aralkyl.“Ring system substituent” may also mean a single moiety whichsimultaneously replaces two available hydrogens on two adjacent carbonatoms (one H on each carbon) on a ring system. Examples of such moietyare methylene dioxy, ethylenedioxy, —C(CH₃)₂— and the like which formmoieties such as, for example:

“Heteroarylalkyl” means a heteroaryl moiety as defined above linked viaan alkyl moiety (defined above) to a parent core. Non-limiting examplesof suitable heteroaryls include 2-pyridinylmethyl, quinolinylmethyl andthe like.

“Heterocyclyl” or “heterocycloalkyl” means a non-aromatic saturatedmonocyclic or multicyclic ring system comprising about 3 to about 10ring atoms, preferably about 5 to about 10 ring atoms, in which one ormore of the atoms in the ring system is an element other than carbon,for example nitrogen, oxygen or sulfur, alone or in combination. Thereare no adjacent oxygen and/or sulfur atoms present in the ring system.Preferred heterocyclyls contain about 5 to about 6 ring atoms. Theprefix aza, oxa or thia before the heterocyclyl root name means that atleast a nitrogen, oxygen or sulfur atom respectively is present as aring atom. Any —NH in a heterocyclyl ring may exist protected such as,for example, as an —N(Boc), —N(CBz), —N(Tos) group and the like; suchprotections are also considered part of this invention. The heterocyclylcan be optionally substituted by one or more “ring system substituents”which may be the same or different, and are as defined herein. Thenitrogen or sulfur atom of the heterocyclyl can be optionally oxidizedto the corresponding N-oxide, S-oxide or S,S-dioxide. Non-limitingexamples of suitable monocyclic heterocyclyl rings include piperidyl,pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, thiazolidinyl,1,4-dioxanyl, tetrahydrofuranyl, tetrahydrothiophenyl, lactam, lactone,and the like. “Heterocyclyl” also includes rings wherein ═O replaces twoavailable hydrogens on the same carbon atom on a ring system (i.e.,heterocyclyl includes rings having a carbonyl in the ring). An exampleof such moiety is pyrrolidone:

“Heterocyclylalkyl” (or “heterocycloalkylalkyl”) means a heterocyclylmoiety as defined above linked via an alkyl moiety (defined above) to aparent core. Non-limiting examples of suitable heterocyclylalkylsinclude piperidinylmethyl, piperazinylmethyl and the like.

“Heterocyclenyl” (or “heterocycloalkenyl”) means a non-aromaticmonocyclic or multicyclic ring system comprising about 3 to about 10ring atoms, preferably about 5 to about 10 ring atoms, in which one ormore of the atoms in the ring system is an element other than carbon,for example nitrogen, oxygen or sulfur atom, alone or in combination,and which contains at least one carbon-carbon double bond orcarbon-nitrogen double bond. There are no adjacent oxygen and/or sulfuratoms present in the ring system, Preferred heterocyclenyl rings containabout 5 to about 6 ring atoms. The prefix aza, oxa or thia before theheterocyclenyl root name means that at least a nitrogen, oxygen orsulfur atom respectively is present as a ring atom. The heterocyclenylcan be optionally substituted by one or more ring system substituents,wherein “ring system substituent” is as defined above. The nitrogen orsulfur atom of the heterocyclenyl can be optionally oxidized to thecorresponding N-oxide, S-oxide or S,S-dioxide. Non-limiting examples ofsuitable heterocyclenyl groups include 1,2,3,4-tetrahydropyridinyl,1,2-dihydropyridinyl, 1,4-dihydropyridinyl, 1,2,3,6-tetrahydropyridinyl,1,4,5,6-tetrahydropyrimidinyl, 2-pyrrolinyl, 3-pyrrolinyl,2-imidazolinyl, 2-pyrazolinyl, dihydroimidazolyl, dihydrooxazolyl,dihydrooxadiazolyl, dihydrothiazolyl, 3,4-dihydro-2H-pyranyl,dihydrofuranyl, fluorodihydrofuranyl, 7-oxabicyclo[2.2.1]heptenyl,dihydrothiophenyl, dihydrothiopyranyl, and the like. “Heterocyclenyl”also includes rings wherein ═O replaces two available hydrogens on thesame carbon atom on a ring system (i.e., heterocyclyl includes ringshaving a carbonyl in the ring). An example of such moiety ispyrrolidinone:

“Heterocyclenylalkyl” (or “heterocycloalkenylalkyl”) means aheterocyclenyl moiety as defined above linked via an alkyl moiety(defined above) to a parent core.

It should be noted that in hetero-atom containing ring systems of thisinvention, there are no hydroxyl groups on carbon atoms adjacent to a N,O or S, as well as there are no N or S groups on carbon adjacent toanother heteroatom. Thus, for example, in the ring:

there is no —OH attached directly to carbons marked 2 and 5.

It should also be noted that tautomeric forms such as, for example, themoieties:

are considered equivalent in certain embodiments of this invention.

“Alkynylalkyl” means an alkynyl-alkyl-group in which the alkynyl andalkyl are as previously described. Preferred alkynylalkyls contain alower alkynyl and a lower alkyl group. The bond to the parent moiety isthrough the alkyl. Non-limiting examples of suitable alkynylalkyl groupsinclude propargylmethyl.

“Heteroaralkyl” means a heteroaryl-alkyl-group in which the heteroaryland alkyl are as previously described. Preferred heteroaralkyls containa lower alkyl group. Non-limiting examples of suitable aralkyl groupsinclude pyridylmethyl, and quinolin-3-ylmethyl. The bond to the parentmoiety is through the alkyl.

“Hydroxyalkyl” means a HO-alkyl-group in which alkyl is as previouslydefined. Preferred hydroxyalkyls contain lower alkyl. Non-limitingexamples of suitable hydroxyalkyl groups include hydroxymethyl and2-hydroxyethyl.

“Acyl” means an H—C(O)—, alkyl-C(O)— or cycloalkyl-C(O)—, group in whichthe various groups are as previously described. The bond to the parentmoiety is through the carbonyl. Preferred acyls contain a lower alkyl.Non-limiting examples of suitable acyl groups include formyl, acetyl andpropanoyl.

“Aroyl” means an aryl-C(O)— group in which the aryl group is aspreviously described. The bond to the parent moiety is through thecarbonyl. Non-limiting examples of suitable groups include benzoyl and1-naphthoyl.

“Alkoxy” means an alkyl-O— group in which the alkyl group is aspreviously described. Non-limiting examples of suitable alkoxy groupsinclude methoxy, ethoxy, n-propoxy, isopropoxy and n-butoxy. The bond tothe parent moiety is through the ether oxygen.

“Aryloxy” means an aryl-O— group in which the aryl group is aspreviously described. Non-limiting examples of suitable aryloxy groupsinclude phenoxy and naphthoxy. The bond to the parent moiety is throughthe ether oxygen.

“Aralkyloxy” means an aralkyl-O— group in which the aralkyl group is aspreviously described. Non-limiting examples of suitable aralkyloxygroups include benzyloxy and 1- or 2-naphthalenemethoxy. The bond to theparent moiety is through the ether oxygen.

“Alkylthio” means an alkyl-S— group in which the alkyl group is aspreviously described. Non-limiting examples of suitable alkylthio groupsinclude methylthio and ethylthio. The bond to the parent moiety isthrough the sulfur.

“Arylthio” means an aryl-S— group in which the aryl group is aspreviously described. Non-limiting examples of suitable arylthio groupsinclude phenylthio and naphthylthio. The bond to the parent moiety isthrough the sulfur.

“Aralkylthio” means an aralkyl-S— group in which the aralkyl group is aspreviously described. Non-limiting example of a suitable aralkylthiogroup is benzylthio. The bond to the parent moiety is through thesulfur.

“Alkoxycarbonyl” means an alkyl-O—CO— group. Non-limiting examples ofsuitable alkoxycarbonyl groups include methoxycarbonyl andethoxycarbonyl. The bond to the parent moiety is through the carbonyl.

“Aryloxycarbonyl” means an aryl-O—C(O)— group. Non-limiting examples ofsuitable aryloxycarbonyl groups include phenoxycarbonyl andnaphthoxycarbonyl. The bond to the parent moiety is through thecarbonyl.

“Aralkoxycarbonyl” means an aralkyl-O—C(O)— group. Non-limiting exampleof a suitable aralkoxycarbonyl group is benzyloxycarbonyl. The bond tothe parent moiety is through the carbonyl.

“Alkylsulfonyl” means an alkyl-S(O₂)— group. Preferred groups are thosein which the alkyl group is lower alkyl. The bond to the parent moietyis through the sulfonyl.

“Arylsulfonyl” means an aryl-S(O₂)— group. The bond to the parent moietyis through the sulfonyl.

The term “substituted” means that one or more hydrogens on thedesignated atom is replaced with a selection from the indicated group,provided that the designated atom's normal valency under the existingcircumstances is not exceeded, and that the substitution results in astable compound. Combinations of substituents and/or variables arepermissible only if such combinations result in stable compounds. By“stable compound” or “stable structure” is meant a compound that issufficiently robust to survive isolation to a useful degree of purityfrom a reaction mixture, and formulation into an efficacious therapeuticagent.

The term “optionally substituted” means optional substitution with thespecified groups, radicals or moieties.

The term “purified”, “in purified form” or “in isolated and purifiedform” for a compound refers to the physical state of said compound afterbeing isolated from a synthetic process (e.g. from a reaction mixture),or natural source or combination thereof. Thus, the term “purified”, “inpurified form” or “in isolated and purified form” for a compound refersto the physical state of said compound after being obtained from apurification process or processes described herein or well known to theskilled artisan (e.g., chromatography, recrystallization and the like),in sufficient purity to be characterizable by standard analyticaltechniques described herein or well known to the skilled artisan.

It should also be noted that any carbon as well as heteroatom withunsatisfied valences in the text, schemes, examples and Tables herein isassumed to have the sufficient number of hydrogen atom(s) to satisfy thevalences.

When a functional group in a compound is termed “protected”, this meansthat the group is in modified form to preclude undesired side reactionsat the protected site when the compound is subjected to a reaction.Suitable protecting groups will be recognized by those with ordinaryskill in the art as well as by reference to standard textbooks such as,for example, T. W. Greene et al, Protective Groups in organic Synthesis(1991), Wiley, New York.

When any variable (e.g., aryl, heterocycle, R², etc.) occurs more thanone time in any constituent or in Formula I, its definition on eachoccurrence is independent of its definition at every other occurrence.

As used herein, the term “composition” is intended to encompass aproduct comprising the specified ingredients in the specified amounts,as well as any product which results, directly or indirectly, fromcombination of the specified ingredients in the specified amounts.

Prodrugs and solvates of the compounds of the invention are alsocontemplated herein. A discussion of prodrugs is provided in T. Higuchiand V. Stella, Pro-drugs as Novel Delivery Systems (1987) 14 of theA.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design,(1987) Edward B. Roche, ed., American Pharmaceutical Association andPergamon Press. The term “prodrug” means a compound (e.g., a drugprecursor) that is transformed in vivo to yield a compound of Formula(I) or a pharmaceutically acceptable salt, hydrate or solvate of thecompound. The transformation may occur by various mechanisms (e.g., bymetabolic or chemical processes), such as, for example, throughhydrolysis in blood. A discussion of the use of prodrugs is provided byT. Higuchi and W. Stella, “Pro-drugs as Novel Delivery Systems,” Vol. 14of the A.C.S. Symposium Series, and in Bioreversible Carriers in DrugDesign, ed. Edward B. Roche, American Pharmaceutical Association andPergamon Press, 1987.

For example, if a compound of Formula (I) or a pharmaceuticallyacceptable salt, hydrate or solvate of the compound contains acarboxylic acid functional group, a prodrug can comprise an ester formedby the replacement of the hydrogen atom of the acid group with a groupsuch as, for example, (C₁-C₈)alkyl, (C₂-C₁₂)alkanoyloxymethyl,1-(alkanoyloxy)ethyl having from 4 to 9 carbon atoms,1-methyl-1-(alkanoyloxy)-ethyl having from 5 to 10 carbon atoms,alkoxycarbonyloxymethyl having from 3 to 6 carbon atoms,1-(alkoxycarbonyloxy)ethyl having from 4 to 7 carbon atoms,1-methyl-1-(alkoxycarbonyloxy)ethyl having from 5 to 8 carbon atoms,N-(alkoxycarbonyl)aminomethyl having from 3 to 9 carbon atoms,1-(N-(alkoxycarbonyl)amino)ethyl having from 4 to 10 carbon atoms,3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl,di-N,N—(C₁-C₂)alkylamino(C₂-C₃)alkyl (such as β-dimethylaminoethyl),carbamoyl-(C₁-C₂)alkyl, N,N-di(C₁-C₂)alkylcarbamoyl-(C₁-C₂)alkyl andpiperidino-, pyrrolidino- or morpholino(C₂-C₃)alkyl, and the like.

Similarly, if a compound of Formula (I) contains an alcohol functionalgroup, a prodrug can be formed by the replacement of the hydrogen atomof the alcohol group with a group such as, for example,(C₁-C₆)alkanoyloxymethyl, 1-((C₁-C₆)alkanoyloxy)ethyl,1-methyl-1-((C₁-C₆)alkanoyloxy)ethyl, (C₁-C₆)alkoxycarbonyloxymethyl,N—(C₁-C₆)alkoxycarbonylaminomethyl, succinoyl, (C₁-C₆)alkanoyl,α-amino(C₁-C₄)alkanyl, arylacyl and α-aminoacyl, orα-aminoacyl-α-aminoacyl, where each α-aminoacyl group is independentlyselected from the naturally occurring L-amino acids, P(O)(OH)₂,—P(O)(O(C₁-C₆)alkyl)₂ or glycosyl (the radical resulting from theremoval of a hydroxyl group of the hemiacetal form of a carbohydrate),and the like.

If a compound of Formula (I) incorporates an amine functional group, aprodrug can be formed by the replacement of a hydrogen atom in the aminegroup with a group such as, for example, R-carbonyl, RO-carbonyl,NRR′-carbonyl where R and R′ are each independently (C₁-C₁₀)alkyl,(C₃-C₇) cycloalkyl, benzyl, or R-carbonyl is a natural α-aminoacyl ornatural α-aminoacyl, —C(OH)C(O)OY¹ wherein Y¹ is H, (C₁-C₆)alkyl orbenzyl, —C(OY²)Y³ wherein Y² is (C₁-C₄)alkyl and Y³ is (C₁-C₆)alkyl,carboxy(C₁-C₆)alkyl, amino(C₁-C₄)alkyl or mono-N— ordi-N,N—(C₁-C₆)alkylaminoalkyl, —C(Y⁴)Y⁵ wherein Y⁴ is H or methyl and Y⁵is mono-N— or di-N,N—(C₁-C₆)alkylamino morpholino, piperidin-1-yl orpyrrolidin-1-yl, and the like.

One or more compounds of the invention may exist in unsolvated as wellas solvated forms with pharmaceutically acceptable solvents such aswater, ethanol, and the like, and it is intended that the inventionembrace both solvated and unsolvated forms. “Solvate” means a physicalassociation of a compound of this invention with one or more solventmolecules. This physical association involves varying degrees of ionicand covalent bonding, including hydrogen bonding. In certain instancesthe solvate will be capable of isolation, for example when one or moresolvent molecules are incorporated in the crystal lattice of thecrystalline solid. “Solvate” encompasses both solution-phase andisolatable solvates. Non-limiting examples of suitable solvates includeethanolates, methanolates, and the like. “Hydrate” is a solvate whereinthe solvent molecule is H₂O.

One or more compounds of the invention may optionally be converted to asolvate. Preparation of solvates is generally known. Thus, for example,M. Caira et al, J. Pharmaceutical Sci., 93(3), 601-611 (2004) describethe preparation of the solvates of the antifungal fluconazole in ethylacetate as well as from water. Similar preparations of solvates,hemisolvate, hydrates and the like are described by E. C. van Tonder etal, AAPS PharmSciTech., 5(1), article 12 (2004); and A. L. Bingham etal, Chem. Commun., 603-604 (2001). A typical, non-limiting, processinvolves dissolving the inventive compound in desired amounts of thedesired solvent (organic or water or mixtures thereof) at a higher thanambient temperature, and cooling the solution at a rate sufficient toform crystals which are then isolated by standard methods. Analyticaltechniques such as, for example I. R. spectroscopy, show the presence ofthe solvent (or water) in the crystals as a solvate (or hydrate).

“Effective amount” or “therapeutically effective amount” is meant todescribe an amount of compound or a composition of the present inventioneffective in inhibiting the above-noted diseases and thus producing thedesired therapeutic, ameliorative, inhibitory or preventative effect.

The compounds of Formula I can form salts which are also within thescope of this invention. Reference to a compound of Formula I herein isunderstood to include reference to salts thereof, unless otherwiseindicated. The term “salt(s)”, as employed herein, denotes acidic saltsformed with inorganic and/or organic acids, as well as basic saltsformed with inorganic and/or organic bases. In addition, when a compoundof Formula I contains both a basic moiety, such as, but not limited to apyridine or imidazole, and an acidic moiety, such as, but not limited toa carboxylic acid, zwitterions (“inner salts”) may be formed and areincluded within the term “salt(s)” as used herein. Pharmaceuticallyacceptable (i.e., non-toxic, physiologically acceptable) salts arepreferred, although other salts are also useful. Salts of the compoundsof the Formula I may be formed, for example, by reacting a compound ofFormula I with an amount of acid or base, such as an equivalent amount,in a medium such as one in which the salt precipitates or in an aqueousmedium followed by lyophilization.

Exemplary acid addition salts include acetates, ascorbates, benzoates,benzenesulfonates, bisulfates, borates, butyrates, citrates,camphorates, camphorsulfonates, fumarates, hydrochlorides,hydrobromides, hydroiodides, lactates, maleates, methanesulfonates,naphthalenesulfonates, nitrates, oxalates, phosphates, propionates,salicylates, succinates, sulfates, tartarates, thiocyanates,toluenesulfonates (also known as tosylates,) and the like. Additionally,acids which are generally considered suitable for the formation ofpharmaceutically useful salts from basic pharmaceutical compounds arediscussed, for example, by P. Stahl et al, Camille G. (eds.) Handbook ofPharmaceutical Salts. Properties, Selection and Use. (2002) Zurich:Wiley-VCH; S. Berge et al, Journal of Pharmaceutical Sciences (1977)66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33201-217; Anderson et al, The Practice of Medicinal Chemistry (1996),Academic Press, New York; and in The Orange Book (Food & DrugAdministration, Washington, D.C. on their website). These disclosuresare incorporated herein by reference thereto.

Exemplary basic salts include ammonium salts, alkali metal salts such assodium, lithium, and potassium salts, alkaline earth metal salts such ascalcium and magnesium salts, salts with organic bases (for example,organic amines) such as dicyclohexylamines, t-butyl amines, and saltswith amino acids such as arginine, lysine and the like. Basicnitrogen-containing groups may be quarternized with agents such as loweralkyl halides (e.g. methyl, ethyl, and butyl chlorides, bromides andiodides), dialkyl sulfates (e.g. dimethyl, diethyl, and dibutylsulfates), long chain halides (e.g. decyl, lauryl, and stearylchlorides, bromides and iodides), aralkyl halides (e.g. benzyl andphenethyl bromides), and others.

All such acid salts and base salts are intended to be pharmaceuticallyacceptable salts within the scope of the invention and all acid and basesalts are considered equivalent to the free forms of the correspondingcompounds for purposes of the invention.

Pharmaceutically acceptable esters of the present compounds include thefollowing groups: (1) carboxylic acid esters obtained by esterificationof the hydroxy groups, in which the non-carbonyl moiety of thecarboxylic acid portion of the ester grouping is selected from straightor branched chain alkyl (for example, acetyl, n-propyl, t-butyl, orn-butyl), alkoxyalkyl (for example, methoxymethyl), aralkyl (forexample, benzyl), aryloxyalkyl (for example, phenoxymethyl), aryl (forexample, phenyl optionally substituted with, for example, halogen,C₁₋₄alkyl, or C₁₋₄alkoxy or amino); (2) sulfonate esters, such as alkyl-or aralkylsulfonyl (for example, methanesulfonyl); (3) amino acid esters(for example, L-valyl or L-isoleucyl); (4) phosphonate esters and (5)mono-, di- or triphosphate esters. The phosphate esters may be furtheresterified by, for example, a C₁₋₂₀ alcohol or reactive derivativethereof, or by a 2,3-di(C₆₋₂₄)acyl glycerol.

Compounds of Formula (I), and salts, solvates, esters and prodrugsthereof, may exist in their tautomeric form (for example, as an amide,enol, keto or imino ether). All such tautomeric forms are contemplatedherein as part of the present invention.

The compounds of Formula (I) may contain asymmetric or chiral centers,and, therefore, exist in different stereoisomeric forms. It is intendedthat all stereoisomeric forms of the compounds of Formula (I) as well asmixtures thereof, including racemic mixtures, form part of the presentinvention. In addition, the present invention embraces all geometric andpositional isomers. For example, if a compound of Formula (I)incorporates a double bond or a fused ring, both the cis- andtrans-forms, as well as mixtures, are embraced within the scope of theinvention.

Diastereomeric mixtures can be separated into their individualdiastereomers on the basis of their physical chemical differences bymethods well known to those skilled in the art, such as, for example, bychromatography and/or fractional crystallization. Enantiomers can beseparated by converting the enantiomeric mixture into a diastereomericmixture by reaction with an appropriate optically active compound (e.g.,chiral auxiliary such as a chiral alcohol or Mosher's acid chloride),separating the diastereomers and converting (e.g., hydrolyzing) theindividual diastereomers to the corresponding pure enantiomers. Also,some of the compounds of Formula (I) may be atropisomers (e.g.,substituted biaryls) and are considered as part of this invention.Enantiomers can also be separated by use of chiral HPLC column.

It is also possible that the compounds of Formula (I) may exist indifferent tautomeric forms, and all such forms are embraced within thescope of the invention. Also, for example, all keto-enol andimine-enamine forms of the compounds are included in the invention.

All stereoisomers (for example, geometric isomers, optical isomers andthe like) of the present compounds (including those of the salts,solvates, esters and prodrugs of the compounds as well as the salts,solvates and esters of the prodrugs), such as those which may exist dueto asymmetric carbons on various substituents, including enantiomericforms (which may exist even in the absence of asymmetric carbons),rotameric forms, atropisomers, and diastereomeric forms, arecontemplated within the scope of this invention, as are positionalisomers (such as, for example, 4-pyridyl and 3-pyridyl). (For example,if a compound of Formula (I) incorporates a double bond or a fused ring,both the cis- and trans-forms, as well as mixtures, are embraced withinthe scope of the invention. Also, for example, all keto-enol andimine-enamine forms of the compounds are included in the invention.)Individual stereoisomers of the compounds of the invention may, forexample, be substantially free of other isomers, or may be admixed, forexample, as racemates or with all other, or other selected,stereoisomers. The chiral centers of the present invention can have theS or R configuration as defined by the IUPAC 1974 Recommendations. Theuse of the terms “salt”, “solvate”, “ester”, “prodrug” and the like, isintended to equally apply to the salt, solvate, ester and prodrug ofenantiomers, stereoisomers, rotamers, tautomers, positional isomers,racemates or prodrugs of the inventive compounds.

The present invention also embraces isotopically-labelled compounds ofthe present invention which are identical to those recited herein, butfor the fact that one or more atoms are replaced by an atom having anatomic mass or mass number different from the atomic mass or mass numberusually found in nature. Examples of isotopes that can be incorporatedinto compounds of the invention include isotopes of hydrogen, carbon,nitrogen, oxygen, phosphorus, fluorine and chlorine and iodine, such as²H, ³H, ¹¹C, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³¹P, ³²P, ³⁵S, ¹⁸F, ³⁶Cl and ¹²³I,respectively.

Certain isotopically-labelled compounds of Formula (I) (e.g., thoselabeled with ³H and ¹⁴C) are useful in compound and/or substrate tissuedistribution assays. Tritiated (i.e., ³H) and carbon-14 (i.e., ¹⁴C)isotopes are particularly preferred for their ease of preparation anddetectability. Certain isotopically-labelled compounds of Formula (I)can be useful for medical imaging purposes. E.g., those labeled withpositron-emitting isotopes like ¹¹C or ¹⁸F can be useful for applicationin Positron Emission Tomography (PET) and those labeled with gamma rayemitting isotopes like ¹²³I can be useful for application in Singlephoton emission computed tomography (SPECT). Further, substitution withheavier isotopes such as deuterium (i.e., ²H) may afford certaintherapeutic advantages resulting from greater metabolic stability (e.g.,increased in vivo half-life or reduced dosage requirements) and hencemay be preferred in some circumstances. Further, substitution withheavier isotopes such as deuterium (i.e., ²H) may afford certaintherapeutic advantages resulting from greater metabolic stability (e.g.,increased in vivo half-life or reduced dosage requirements) and hencemay be preferred in some circumstances. Additionally, isotopicsubstitution at a site where epimerization occurs may slow or reduce theepimerization process and thereby retain the more active or efficaciousform of the compound for a longer period of time. Isotopically labeledcompounds of Formula (I), in particular those containing isotopes withlonger half lives (T½>1 day), can generally be prepared by followingprocedures analogous to those disclosed in the Schemes and/or in theExamples herein below, by substituting an appropriate isotopicallylabeled reagent for a non-isotopically labeled reagent.

Polymorphic forms of the compounds of Formula (I), and of the salts,solvates, esters and prodrugs of the compounds of Formula (I), areintended to be included in the present invention.

The compounds according to the invention can have pharmacologicalproperties; in particular, the compounds of Formula (I) can bemodulators of gamma secretase (including inhibitors, antagonists and thelike).

More specifically, the compounds of Formula (I) can be useful in thetreatment of a variety of disorders of the central nervous systemincluding, for example, including, but not limited to, Alzheimer'sdisease, AIDS-related dementia, Parkinson's disease, amyotrophic lateralsclerosis, retinitis pigmentosa, spinal muscular atrophy and cerebellardegeneration and the like.

Another aspect of this invention is a method of treating a mammal (e.g.,human) having a disease or condition of the central nervous system byadministering a therapeutically effective amount of at least onecompound of Formula (I), or a pharmaceutically acceptable salt, solvate,ester or prodrug of said compound to the mammal.

A preferred dosage is about 0.001 to 500 mg/kg of body weight/day of thecompound of Formula (I). An especially preferred dosage is about 0.01 to25 mg/kg of body weight/day of a compound of Formula I, or apharmaceutically acceptable salt or solvate of said compound.

The compounds of this invention may also be useful in combination(administered together or sequentially) with one or more additionalagents listed above.

The compounds of this invention may also be useful in combination(administered together or sequentially) with one or more compoundsselected from the group consisting of Aβ antibody inhibitors, gammasecretase inhibitors and beta secretase inhibitors.

If formulated as a fixed dose, such combination products employ thecompounds of this invention within the dosage range described herein andthe other pharmaceutically active agent or treatment within its dosagerange.

Accordingly, in an aspect, this invention includes combinationscomprising an amount of at least one compound of Formula (I), or apharmaceutically acceptable salt, solvate, ester or prodrug thereof, andan amount of one or more additional agents listed above wherein theamounts of the compounds/treatments result in desired therapeuticeffect.

The pharmacological properties of the compounds of this invention may beconfirmed by a number of pharmacological assays. Certain assays areexemplified later in this document.

This invention is also directed to pharmaceutical compositions whichcomprise at least one compound of Formula (I), or a pharmaceuticallyacceptable salt, solvate, ester or prodrug of said compound and at leastone pharmaceutically acceptable carrier.

For preparing pharmaceutical compositions from the compounds describedby this invention, inert, pharmaceutically acceptable carriers can beeither solid or liquid. Solid form preparations include powders,tablets, dispersible granules, capsules, cachets and suppositories. Thepowders and tablets may be comprised of from about 5 to about 95 percentactive ingredient. Suitable solid carriers are known in the art, e.g.,magnesium carbonate, magnesium stearate, talc, sugar or lactose.Tablets, powders, cachets and capsules can be used as solid dosage formssuitable for oral administration. Examples of pharmaceuticallyacceptable carriers and methods of manufacture for various compositionsmay be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences,18^(th) Edition, (1990), Mack Publishing Co., Easton, Pa.

Liquid form preparations include solutions, suspensions and emulsions.As an example may be mentioned water or water-propylene glycol solutionsfor parenteral injection or addition of sweeteners and opacifiers fororal solutions, suspensions and emulsions. Liquid form preparations mayalso include solutions for intranasal administration.

Aerosol preparations suitable for inhalation may include solutions andsolids in powder form, which may be in combination with apharmaceutically acceptable carrier, such as an inert compressed gas,e.g. nitrogen.

Also included are solid form preparations that are intended to beconverted, shortly before use, to liquid form preparations for eitheroral or parenteral administration. Such liquid forms include solutions,suspensions and emulsions.

The compounds of the invention may also be deliverable transdermally.The transdermal compositions can take the form of creams, lotions,aerosols and/or emulsions and can be included in a transdermal patch ofthe matrix or reservoir type as are conventional in the art for thispurpose.

The compounds of this invention may also be delivered subcutaneously.

Preferably the compound is administered orally.

Preferably, the pharmaceutical preparation is in a unit dosage form. Insuch form, the preparation is subdivided into suitably sized unit dosescontaining appropriate quantities of the active component, e.g., aneffective amount to achieve the desired purpose.

The quantity of active compound in a unit dose of preparation may bevaried or adjusted from about 1 mg to about 100 mg, preferably fromabout 1 mg to about 50 mg, more preferably from about 1 mg to about 25mg, according to the particular application.

The actual dosage employed may be varied depending upon the requirementsof the patient and the severity of the condition being treated.Determination of the proper dosage regimen for a particular situation iswithin the skill of the art. For convenience, the total daily dosage maybe divided and administered in portions during the day as required.

The amount and frequency of administration of the compounds of theinvention and/or the pharmaceutically acceptable salts thereof will beregulated according to the judgment of the attending clinicianconsidering such factors as age, condition and size of the patient aswell as severity of the symptoms being treated. A typical recommendeddaily dosage regimen for oral administration can range from about 1mg/day to about 500 mg/day, preferably 1 mg/day to 200 mg/day, in two tofour divided doses.

Another aspect of this invention is a kit comprising a therapeuticallyeffective amount of at least one compound of Formula (I), or apharmaceutically acceptable salt, solvate, ester or prodrug of saidcompound and a pharmaceutically acceptable carrier, vehicle or diluent.

Yet another aspect of this invention is a kit comprising an amount of atleast one compound of Formula (I), or a pharmaceutically acceptablesalt, solvate, ester or prodrug of said compound and an amount of atleast one additional agent listed above, wherein the amounts of the twoor more ingredients result in desired therapeutic effect.

The invention disclosed herein is exemplified by the followingillustrative schemes and examples which should not be construed to limitthe scope of the disclosure. Alternative mechanistic pathways andanalogous structures will be apparent to those skilled in the art.

Example 1

Step 1

TBDMSCl (10.5 g, 70 mmol) was added to a solution of 1 (5.0 g, 67 mmol),triethylamine (9 ml, 67 mmol) and DMAP (500 mg, 4.1 mmol) in methylenechloride (80 mL), and the reaction solution was stirred at roomtemperature for 12 hours. Water was added and the layers were separated.The aqueous phase was extracted with ethyl acetate, the organic phasewas dried over anhydrous sodium sulfate and concentrated under reducedpressure to obtain 10.6 g of product 2.

Step 2

Triethylamine (34 g, 336 mmol) was added to a solution of 2 (10.0 g,52.8 mmol) and 4′-fluoro acetophenone (6.64 g, 48.0 mmol) in a mixtureof DMF (48 mL) and DCM (13 mL). The reaction solution was cooled to 0°C. and a solution of titanium(IV) chloride (8.7 g, 45.6 mmol) in DCM (5mL) was added dropwise over 30 minute period. The resulting solution wasstirred at 40° C. for one hour, then at room temperature for 12 hours.Diluted with ether, clarified by filtration and the filtrate was washedwith cold water, brine and dried over anhydrous sodium sulfate. Thesolvent was removed under reduced pressure to give 14.3 g of product 3.

Step 3

A solution of N-Bromosuccinamide (3.6 g, 20.5 mmol) in DMF (20 mL) wasadded dropwise to a solution of diethyl 2-(hydroxyimino)-ethylphsphonate(4.0 g, 20.5 mmol) [Bioorganic & Medicinal Chemistry Letters, 15(1),231-234; 2005] in DMF (50 mL) at −20° C. overl 5 minutes. The reactionsolution was stirred at −20° C. for 30 minutes, then allowed to slowlywarm to 0° C. and kept at that temperature for two hours. A mixture of 3(6.3 g 20.5 mmol) and triethylamine (2.1 g, 20.5 mmol) in DCM (25 mL)was slowly added and the reaction solution was stirred at roomtemperature for 12 hours. The solvent was removed at reduced pressureand the residue was dissolved in ethyl acetate. The organic phase waswashed with brine, dried over anhydrous sodium sulfate and concentratedat reduced pressure. The residue was purified by column chromatographyusing Silica Gel (hexane:ethyl acetate=100:0 to 0:100) to obtain 1.53 gof product 4.

Step 4

NBS (383 mg, 2.2 mmol) was added to a solution of 4 (760 mg, 2.0 mmol)in CCl4 (15 mL), and the reaction solution was stirred at roomtemperature for one hour. A catalytic amount of benzoyl peroxide (48 mg,0.2 mmol) was added and the reaction solution was stirred at 60° C. for12 hours. The reaction solution was clarified by filtration and thefiltrate was concentrated under reduced pressure. The residue wasdiluted with ethyl acetate, washed with saturated solution of sodiumthiosulfate, and brine. The organic phase was dried over anhydroussodium sulfate and concentrated under reduced pressure to obtain 955 mgof product 5 as a 1:1 mixture, which was used as is in the nextreaction.

Step 5

To a solution of 5 (860 mg, 1.5 mmol) and 6 (318 mg, 1.5 mmol) [US2007/0219181 A1, page 62] in THF (20 mL) at room temperature was addedsodium hydride (90 mg, 2.3 mmol, 60%) all at once, and the reactionsolution was stirred at room temperature for 12 hours. The reactionsolution was quenched with water, and extracted with ethyl acetate. Theorganic phase was dried over anhydrous sodium sulfate and concentratedunder reduced pressure. The residue was dissolved in DMF (10 mL) andtreated with sodium hydride (90 mg, 2.3 mmol, 60%). The reactionsolution was stirred at room temperature for one hour before it wasquenched with water. The layers ware separated and the organic layer waswashed with water, dried over anhydrous sodium sulfate and concentrated.The residue was purified by column chromatography using Silica Gel(hexane:triethylamine=99:1) to obtain 426 mg of products 7.

Step 6

Tetrabutylammonium fluoride (2.5 mL, 1M THF) was added to ice-coldsolution of 7 (400 mg, 0.71 mmol) in THF (10 mL), and the reactionsolution was stirred at 0° C. for 12 hours. The reaction solution wasconcentrated under reduced pressure, and the residue was diluted withethyl acetate. The organic phase was washed with 0.5 N HCl, dried overanhydrous magnesium sulfate and concentrated at reduced pressure. Theresidue was purified by column chromatography using Silica Gel(hexane:ethyl acetate=100:0 to 0:100) to obtain 141 mg of product 8.

Step 7

To a solution of 8 (32 mg, 0.07 mmol) in CHCl3 (2 mL) wad addedmercury(II) trifluoroatetae (31 mg, 0.07 mmol) and the reaction mixturestirred at room temperature for 12 hours. The crude was purified bycolumn chromatography using Silica Gel (methanol:ethyl acetae=10:90) toobtain 10 mg of product 9.

Compound 9:

¹H-NMR (CDCl₃) δ (ppm): 7.73 (s, 1H), 7.53 (m, 2H), 7.28 (m, 3H), 7.11(m, 2H), 6.93 (s, 1H), 5.93 (s, 1H), 4.55 (m, 1H), 3.85 (s, 3H), 3.13(m, 2H), 2.30 (s, 3H), 1.90 (s, 3H), 1.45 (d, 3H, J=6.4 Hz). MS(ES-LCMS, M+1) 449.

Example 2

Step a

To the solution of 10 (15 g, 85.5 mmol) in 300 ml of anhydrous CH₂Cl₂ at0° C. was slowly added Et₃N (26 ml, 188.2 mmol). The cooling bath wasremoved, TMSCl (24 ml, 188.2 mmol) was slowly added to the mixture.After stirring at r.t. for 24 h, additional Et₃N (12 ml, 85.5 mmol) andTMSCl (11 ml, 85.5 mmol) were added. The mixture was stirred at r.t. foranother 24 h. The solvent was removed, the product was dissolved in 500ml of ether, filtered through the celite, and concentrated to give 22.5g of 11, yield: 82%.

Step b

To the solution of 11 (22.5 g, 70.4 mmol) and ethyl3,5-difluorobenzoylformate (11.5 g, 53.7 mmol) in 180 ml of anhydrous1,2-dichloroethane was added TMSTf (0.5 ml, 2.69 mmol) at r.t. Afterstirring at 85° C. for 24 h, the solvent was removed, the product wasdissolved in 500 ml of ether, washed with H₂O (2×200 ml), and brine,dried over Na₂SO₄, filtered and concentrated to give 22 g of 12, yield:100%.

Step c

57 g of the title compound 13 was obtained from 12 (12 g) in the samemanner as in Example 1, steps 3 and 4.

Step d

To the solution of 13 (3.6 g, 5.10 mmol) in 50 ml of MeOH was added1-choloethyl chloroformate (0.83 ml, 7.65 mmol). After stirring at r.t.for 0.5 h, the solvent was removed, the product was purified by Iscousing 5% of MeOH/CH₂Cl₂ to give 2.8 g of 14, yield: 93%. MH⁺: 591.04.

Step e

To the solution of 14 (0.18 g, 0.304 mmol) in 4 ml of anhydrous THF/DMF(1:1) was added NaH (0.026 g, 0.638 mmol) at 0° C. After stirring at 0°C. for 45 minutes, additional NaH (0.012 g, 0.304 mmol) was added, andthe mixture was stirred at 0° C. for additional 1.5 h. THF was removed,the residue was dissolved in DMF, filtered, and purified byreverse-phase HPLC to give 0.1 g of compound 15 and 16 MH⁺: 483.3, totalyield for 15 and 16: 68%.

Step f

To the solution of 15 and 16 (0.092 g, 0.19 mmol) in 5 ml oftoluene/MeOH (4:1) was added TMSCHN₂ (0.2 ml, 0.38 mmol). After stirringat r.t. for 24 h, the solvent was removed; the residue was purified byIsco using 5% of MeOH/CH₂Cl₂ to give 0.075 g of 17 and 18, yield: 80%,followed by reverse-phase HPLC to give 0.033 g of 17 and 0.027 g of 18MH⁺: 497.3.

Step g

To the solution of 18 (0.026 g, 0.052 mmol) in 3 ml of EtOH/MeOH (1:1)was added NaBH₄ (0.008 g, 0.21 mmol). After stirring at r.t. for 1 h,the solvent was removed; the residue was purified by Isco using 5% ofMeOH/CH₂Cl₂ to give 0.02 g of 20, yield: 82%, MH⁺: 469.3.

Step h and step i

To the solution of 14 (0.10 g, 0.17 mmol) in 4 ml of anhydrous THF/DMF(1:1) was added LHMDS (0.42, 0.42 mmol) at 0° C. After stirring at 0° C.for 0.5 h, additional LHMDS (0.10 ml, 0.10 mmol) was added, and themixture was stirred at 0° C. for additional 1.5 h. THF was removed, theresidue was extracted with 10% of MeOH/CH₂Cl₂ and NH₄Cl aqueoussolution, dried over Na₂SO₄, filtered. The filtrate was concentrated andtreated with TMSCHN₂ in step g (the same as step d) to give 0.008 g of21, MH⁺: 482.3.

Following procedures similar to those of Examples 1 and 2, the followingcompounds were prepared:

Example 3

4-bromophenyl sulfur pentabromide (5.2 g, 18.4 mmole) was dissolved in50 ml THF and the reaction was cooled to −40° C. Isopropylmagnesiumchloride lithium chloride complex (1.3M in THF, 14.1 ml) was added andthe reaction was stirred for two hours with bath temperature rising to0° C. This solution was then cannulated to Diethyl oxalate (2.68 g, 18.4mmole) in 50 ml THF at −78° C. The reaction was stirred for three hourswith temperature slowly rising to room temperature. 200 ml water and 200ml EtOAc were added. The organic layer was washed with water (2×200 ml),dried over Na₂SO₄ and concentrated. The residue was purified by column(EtOAc/hexane from 0/100 to 25/75 in 45 minutes). Yield: 2.0 g. ¹H NMR(CDCl₃ 400 MHz): 8.16 (d, J=8.8 Hz, 2H), 7.91 (d, J=8.8 Hz, 2H), 4.47(q, J=7.3 Hz, 2H), 1.44 (t, J=7.3 Hz, 3H).

Following a similar procedure the following compound is prepared:

Following these procedures and techniques well known in the art,compounds having —SF₅, —OSF₅ or —Si(R¹⁵)₃ are prepared.

Assay:

Secretase Reaction and Aβ Analysis in Whole Cells: HEK293 cellsoverexpressing APP with Swedish and London mutations were treated withthe specified compounds for 5 hour at 37° C. in 100 ml of DMEM mediumcontaining 10% fetal bovine serum. At the end of the incubation, totalAβ, Aβ40 and Aβ42 were measured using electrochemiluminescence (ECL)based sandwich immunoassays.

Total Aβ was determined using a pair of antibodies TAG-W02 andbiotin-4G8, Aβ40 was identified with antibody pairs TAG-G2-10 andbiotin-4G8, while Aβ42 was identified with TAG-G2-11 and biotin-4G8. TheECL signal was measured using Sector Imager 2400 (Meso Scale Discovery).

MS Analysis of Aβ Profile: Aβ profile in conditioned media wasdetermined using surface enhanced laser desorption/ionization (SELDI)mass spectrometry. Conditioned media was incubated with antibody W02coated PS20 ProteinChip array. Mass spectra of Aβ captured on the arraywere read on SELDI ProteinChip Reader (Bio-Rad) according tomanufacture's instructions.

CSF Aβ Analysis: Aβ in rat CSF was determined using MSD technology asdescribed above. Aβ40 was measured using antibody pair Tag-G2-10 andbiotin-4G8, while Aβ42 was measured using Tag-anti Aβ42 (Meso ScaleDiscovery) and biotin-4G8. The ECL signal was measured using SectorImager 2400 (Meso Scale Discovery).

Matrix-assisted laser desorption/ionization mass spectrometric (MALDIMS) analysis of Aβ is performed on a Voyager-DE STR mass spectrometer(ABI, Framingham, Mass.). The instrument is equipped with a pulsednitrogen laser (337 nm). Mass spectra are acquired in the linear modewith an acceleration voltage of 20 kV. Each spectrum presented in thiswork represents an average of 256 laser shots. To prepare thesample-matrix solution, 1 μL of immunoprecipitated Aβ sample is mixedwith 3 μL of saturated α-cyano-4-hydroxycinnamic acid solution in 0.1%TFA/acetonitrile. The sample-matrix solution is then applied to thesample plate and dried at ambient temperature prior to massspectrometric analysis. All the spectra are externally calibrated with amixture of bovine insulin and ACTH (18-39 clip).

Compounds 15 to 26 had an Aβ42 IC₅₀ within the range of about 51 toabout 13932 nM.

While the present invention has been described in conjunction with thespecific embodiments set forth above, many alternatives, modificationsand other variations thereof will be apparent to those of ordinary skillin the art. All such alternatives, modifications and variations areintended to fall within the spirit and scope of the present invention.

1-44. (canceled)
 45. A compound of the formula (I):

or a pharmaceutically acceptable salt thereof, wherein: G, U, R⁶, R⁷,R⁹, and R¹⁰, are independently selected; letters (A) and (B) in formula(I) are reference letters to identify the rings present in formula (I);G is selected from the group consisting of: C(O), O and S; U is CR⁵ orN; the dotted line in Ring (B) represents an optional bond; Ring (B) isa 5 to 8 membered ring (including the atoms common to Ring (A)), and:(1) when U is CR⁵ said Ring (B) optionally comprising 1 to 2 heteroatomsindependently selected from the group consisting of O, NR² and S, and(2) when U is N said Ring (B) optionally comprises 1 to 2 additionalheteroatoms independently selected from the group consisting of O, NR²and S; and said Ring (B) is optionally substituted with 1 to 5independently selected R²¹ groups; R⁵ is selected from the groupconsisting of: H, alkyl-, alkenyl- and alkynyl-, aryl-, arylalkyl-,alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-,heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-; and wherein eachof said R⁵ alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-, alkylaryl-,cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-,heterocyclyl- and heterocyclyalkyl-groups are optionally substitutedwith 1-5 independently selected R²¹ substituents; R⁶ and R⁷ are eachindependently selected from the group consisting of: H, —C(O)R¹⁵,—C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, alkyl-, alkenyl- andalkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-,heteroaryl-, heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-,benzofusedcycloalkyl, fused benzoheterocycloalkyl, fusedheteroarylcycloalkyl, fused heteroarylheterocycloalkyl; and wherein eachof said R⁶ and R⁷ alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-,alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-,heteroarylalkyl-, heterocyclyl-, heterocyclyalkyl-,benzofusedcycloalkyl, fused benzoheterocycloalkyl, fusedheteroarylcycloalkyl, and fused heteroarylheterocycloalkyl group isoptionally substituted with 1-5 independently selected R²¹ substituents;or R⁶ and R⁷, taken together with the carbon atom to which they arebound, form a spirocyclic carbocyclic moiety or a spirocyclicheterocyclic moiety, and: (a) optionally, said spirocyclic carbocyclicmoiety is substituted with 1-4 independently selected R²¹ substituents,(b) optionally, said spirocyclic heterocyclic moiety is substituted with1-4 independently selected R²¹ substituents, (c) optionally, saidspirocyclic carbocyclic moiety is fused with an aryl, heteroaryl,cycloalkyl, or heterocycloalkyl ring to form a fused ring moiety, andoptionally, each ring of said fused ring moiety is substituted with 1-4independently selected R²¹ substituents; (d) optionally, saidspirocyclic heterocyclic moiety is fused with an aryl, heteroaryl,cycloalkyl, or heterocycloalkyl ring to form a fused ring moiety, andoptionally, each ring of said fused ring moiety is substituted with 1-4independently selected R²¹ substituents; R⁹ is selected from the groupconsisting of: alkyl-, alkenyl-, alkynyl-, aryl-, arylalkyl-,alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-,heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, and, optionally,each R⁹ group is substituted with 1-3 independently selected R²¹ groups;R¹⁰ is selected from the group consisting of a bond, alkyl-, alkenyl-,alkynyl-, aryl-, arylalkyl-, alkylaryl-, cycloalkyl-, cycloalkylalkyl-,heteroaryl-, heteroarylalkyl-, heterocyclyl-, heterocyclyalkyl-,

wherein X is selected from the group consisting of: O, N(R¹⁴) or S; and,optionally, each of said R¹⁰ groups are substituted with 1-3independently selected R²¹ substitutents; R⁹ is selected from the groupconsisting of alkyl-, alkenyl- and alkynyl-, aryl-, arylalkyl-,alkylaryl-, cycloalkyl-, cycloalkylalkyl-, heteroaryl-,heteroarylalkyl-, heterocyclyl- and heterocyclyalkyl-, wherein each ofsaid alkyl-, alkenyl- and alkynyl-, aryl-, arylalkyl-, alkylaryl-,cycloalkyl-, cycloalkylalkyl-, heteroaryl-, heteroarylalkyl-,heterocyclyl- and heterocyclyalkyl- can be unsubstituted or optionallyindependently substituted with 1-3 substituents which can be the same ordifferent, each substituent being independently selected from the groupconsisting of the moieties shown below; R¹⁴ is selected from the groupconsisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,cycloalkenyl, heterocyclyl, heterocyclenyl, heterocyclylalkyl,heterocyclyalkenyl-, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —CN,—C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —S(O)N(R¹⁵)(R¹⁶),—S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, and —P(O)(OR¹⁵)(OR¹⁶); and whereineach of the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,cycloalkenyl, heterocyclyl, heterocyclenyl, heterocyclylalkyl,heterocyclyalkenyl-, aryl, arylalkyl, heteroaryl, and heteroarylalkylgroups in are independently unsubstituted or substituted by 1 to 5 R²¹group; Each R^(15A) is independently selected from the group consistingof alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,arylcycloalkyl, arylheterocyclyl, (R¹⁸)₁₋₅-alkyl, (R¹⁸)₁₋₅-cycloalkyl,(R¹⁸)₁₋₅-cycloalkylalkyl, (R¹⁸)₁₋₅-heterocyclyl,(R¹⁸)₁₋₅-heterocyclylalkyl, (R¹⁸)₁₋₅-aryl, (R¹⁸)₁₋₅-arylalkyl,(R¹⁸)₁₋₅-heteroaryl and (R¹⁸)₁₋₅-heteroarylalkyl; and wherein each R¹⁸in each group can be on any substitutable atom; Each R^(16A) isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl,aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl,arylheterocyclyl, (R¹⁸)₁₋₅-alkyl, (R¹⁸)₁₋₅-cycloalkyl,(R¹⁸)₁₋₅-cycloalkylalkyl, (R¹⁸)₁₋₅-heterocyclyl,(R¹⁸)₁₋₅-heterocyclylalkyl, (R¹⁸)₁₋₅-aryl, (R¹⁸)₁₋₅-arylalkyl,(R¹⁸)₁₋₅-heteroaryl and (R¹⁸)₁₋₅-heteroarylalkyl; and wherein each R¹⁸in each group can be on any substitutable atom; R¹⁵, R¹⁶ and R¹⁷ areindependently selected from the group consisting of H, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl,aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylcycloalkyl,arylheterocyclyl, (R¹⁸)₁₋₅-alkyl, (R¹⁸)₁₋₅-cycloalkyl,(R¹⁸)₁₋₅-cycloalkylalkyl, (R¹⁸)₁₋₅-heterocyclyl,(R¹⁸)₁₋₅-heterocyclylalkyl, (R¹⁸)₁₋₅-aryl, (O)₁₋₅-arylalkyl,(R¹⁸)₁₋₅-heteroaryl and (R¹⁸)₁₋₅-heteroarylalkyl; and wherein each R¹⁸in each group can be on any substitutable atom; Each R¹⁸ isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, —NO₂, halo,heteroaryl, HO-alkyoxyalkyl, —CF₃, —CN, alkyl-CN, —C(O)R¹⁹, —C(O)OH,—C(O)OR¹⁹, —C(O)NHR²⁰, —C(O)NH₂, —C(O)NH₂—C(O)N(alkyl)₂,—C(O)N(alkyl)(aryl), —C(O)N(alkyl)(heteroaryl), —SR¹⁹, —S(O)₂R²⁰,—S(O)NH₂, —S(O)NH(alkyl), —S(O)N(alkyl)(alkyl), —S(O)NH(aryl),—S(O)₂NH₂, —S(O)₂NHR¹⁹, —S(O)₂NH(heterocyclyl), —S(O)₂N(alkyl)₂,—S(O)₂N(alkyl)(aryl), —OCF₃, —OH, —OR²⁰, —O-heterocyclyl,—O-cycloalkylalkyl, —O-heterocyclylalkyl, —NH₂, —NHR²⁰, —N(alkyl)₂,—N(arylalkyl)₂, —N(arylalkyl)-(heteroarylalkyl), —NHC(O)R²⁰, —NHC(O)NH₂,—NHC(O)NH(alkyl), —NHC(O)N(alkyl)(alkyl), —N(alkyl)C(O)NH(alkyl),—N(alkyl)C(O)N(alkyl)(alkyl), —NHS(O)₂R²⁰, —NHS(O)₂NH(alkyl),—NHS(O)₂N(alkyl)(alkyl), —N(alkyl)S(O)₂NH(alkyl) and—N(alkyl)S(O)₂N(alkyl)(alkyl); or, two R¹⁸ moieties on adjacent carbonscan be taken together with the atoms to which they are bound to form:

R¹⁹ is selected from the group consisting of: alkyl, cycloalkyl, aryl,arylalkyl and heteroarylalkyl; R²⁰ is selected from the group consistingof: alkyl, cycloalkyl, aryl, halo substituted aryl, arylalkyl,heteroaryl and heteroarylalkyl; Each R²¹ is independently selected fromthe group consisting of alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkylalkyl,aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, —CN, —OR¹⁵,—C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)(R¹⁶), —SF_(S), —OSF₅, —Si(R^(15A))₃wherein each R^(15A) is independently selected —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶),—CH(R¹⁵)(R¹⁶), —S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶),—N(R¹⁵)(R¹⁶), -alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶,—CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —CH₂—R¹⁵; —CH₂N(R¹⁵)(R¹⁶),—N(R¹⁵)S(O)R^(16A), —N(R¹⁵)S(O)₂R^(16A), —CH₂—N(R¹⁵)S(O)₂R^(16A),—N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷),—CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶,—S(O)R^(15A), —N₃, —NO₂ and —S(O)₂R^(15A); and, optionally, each of saidalkyl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl,heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,alkenyl and alkynyl R²¹ groups are substituted with 1 to 5 independentlyselected R²² groups; and Each R²² is independently selected from thegroup consisting of: alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl,aryl, heteroaryl, halo, —CF₃, —CN, —OR¹⁵, —C(O)R¹⁵, —C(O)OR¹⁵,-alkyl-C(O)OR¹⁵, C(O)N(R¹⁵)(R¹⁶), —SF_(S), —OSF₅, —Si(R^(15A))₃ whereineach R^(15A) is independently selected —SR¹⁵, —S(O)N(R¹⁵)(R¹⁶),—S(O)₂N(R¹⁵)(R¹⁶), —C(═NOR¹⁵)R¹⁶, —P(O)(OR¹⁵)(OR¹⁶), —N(R¹⁵)(R¹⁶),-alkyl-N(R¹⁵)(R¹⁶), —N(R¹⁵)C(O)R¹⁶, —CH₂—N(R¹⁵)C(O)R¹⁶,—N(R¹⁵)S(O)R^(16A), —N(R¹⁵)S(O)₂R^(16A), —CH₂—N(R¹⁵)S(O)₂R^(16A),—N(R¹⁵)S(O)₂N(R¹⁶)(R¹⁷), —N(R¹⁵)S(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)N(R¹⁶)(R¹⁷),—CH₂—N(R¹⁵)C(O)N(R¹⁶)(R¹⁷), —N(R¹⁵)C(O)OR¹⁶, —CH₂—N(R¹⁵)C(O)OR¹⁶, —N₃,═NOR¹⁵, —NO₂, —S(O)R^(15A) and —S(O)₂R^(15A).
 46. The compound of claim45 wherein said R¹⁰ is phenyl substituted with one R²¹ group, and saidR⁹ is imidazolyl substituted with one R²¹ group, wherein each R²¹ isindependently selected.
 47. The compound of claim 45 wherein the R⁹—R¹⁰—moiety is selected from the group consisting of:


48. The compound of claim 45 wherein R⁶ is alkyl, and R⁷ is asubstituted aryl group.
 49. The compound of claim 45 wherein R⁷ is:phenyl, or phenyl substituted with one or more independently selectedR²¹ groups, or phenyl substituted with 1 to 3 independently selected R²¹groups, or phenyl substituted with 1 to 3 R²¹ groups, and each R²¹ groupis the same or different halo, or phenyl substituted with 1 to 3 F, orphenyl substituted with one —CN group, or phenyl substituted with one ortwo —CF₃ groups, or phenyl substituted with R²¹ groups and at least oneR²¹ group selected from the group consisting of: —SF₅, —OSF₅ and—Si(R^(15A))₃, wherein each R^(15A) is independently selected, or phenylsubstituted with R²¹ groups and at least one R²¹ group selected from thegroup consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, and each R^(15A) isthe same or different alkyl group, or phenyl substituted with R²¹ groupsand at least one R²¹ group selected from the group consisting of: —SF₅,—OSF₅ and —Si(R^(15A))₃, and each R^(15A) is the same or different alkylgroup, or phenyl substituted with R²¹ groups and at least one R²¹ groupselected from the group consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃. 50.The compound of claim 45 wherein R⁷ is selected from the groupconsisting of:


51. The compound of claim 45 wherein: (a) G is O and U is CR⁵, (b) G isO and U is N, (c) G is S and U is CR⁵, (d) G is S and U is N, (e) G isC(O) and U is CR⁵, (f) G is C(O) and U is N, (g) G is N(R¹⁴) and LI isCR⁵, or (h) G is G is N(R¹⁴) and U is N.
 52. The compound of claim 45wherein: (a) the R⁹—R¹⁰— moiety is selected from the group consistingof:

(b) R⁶ is alkyl, (c) R⁷ is a substituted aryl group, and (d) G and U areselected from the group consisting of: (i) G is O and U is CR⁵, (ii) Gis O and U is N, (iii) G is S and U is CR⁵, (iv) G is S and U is N, (v)G is C(O) and U is CR⁵, (vi) G is C(O) and U is N, (vii) G is N(R¹⁴) andU is CR⁵, and (viii) G is N(R¹⁴) and U is N.
 53. The compound of claim52 wherein R⁷ is: phenyl, or phenyl substituted with one or moreindependently selected R²¹ groups, or phenyl substituted with 1 to 3independently selected R²¹ groups, or phenyl substituted with 1 to 3 R²¹groups, and each R²¹ group is the same or different halo, or phenylsubstituted with 1 to 3 F, or phenyl substituted with one —CN group, orphenyl substituted with one or two —CF₃ groups, or phenyl substitutedwith R²¹ groups and at least one R²¹ group selected from the groupconsisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, wherein each R^(15A) isindependently selected, or phenyl substituted with R²¹ groups and atleast one R²¹ group selected from the group consisting of: —SF₅, —OSF₅and —Si(R^(15A))₃, and each R^(15A) is the same or different alkylgroup, or phenyl substituted with R²¹ groups and at least one R²¹ groupselected from the group consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃,and each R^(15A) is the same or different alkyl group, or phenylsubstituted with R²¹ groups and at least one R²¹ group selected from thegroup consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃.
 54. The compound ofclaim 53 wherein R⁷ is selected from the group consisting of:


55. The compound of claim 45 wherein the compounds of formula (I) areselected from the group consisting of: 2A, 3A, 4A, 5A, 6A, 7A, 8A, 2B,3B, 4B, 5B, 6B, 7B, 8B, 2C, 3C, 4C, 5C, 6C, 7C, 8C, 2D, 3D, 4D, 5D, 6D,7D, 8D, 2E, 3E, 4E, 5E, 2F, 3F, 4F, 5F, 2G, 3G, 4G, 5G, 2H, 3H, 4H, 5H,2I, 3I, 4I, 5I, 2J, 3J, 4J, 5J, 2K, 3K, 4K, 5K, 2L, 3L, 4LH, 5L, 2M, 3M,4M, 5M, 2N, 3N, 4N, 5N, 2O, 3O, 4O, 5O, 2P, 3P, 4P, and 5P.
 56. Thecompound of claim 45 wherein: R⁶ is alkyl; R⁷ is: phenyl, or phenylsubstituted with one or more independently selected R²¹ groups, orphenyl substituted with 1 to 3 independently selected R²¹ groups, orphenyl substituted with 1 to 3 R²¹ groups, and each R²¹ group is thesame or different halo, or phenyl substituted with 1 to 3 F, or phenylsubstituted with one —CN group, or phenyl substituted with one or two—CF₃ groups, or phenyl substituted with R²¹ groups and at least one R²¹group selected from the group consisting of: —SF₅, —OSF₅ and—Si(R^(15A))₃, wherein each R^(15A) is independently selected, or phenylsubstituted with R²¹ groups and at least one R²¹ group selected from thegroup consisting of: —SF₅, —OSF₅ and —Si(R^(15A))₃, and each R^(15A) isthe same or different alkyl group, or phenyl substituted with R²¹ groupsand at least one R²¹ group selected from the group consisting of: —SF₅,—OSF₅ and —Si(R^(15A))₃, and each R^(15A) is the same or different alkylgroup, or phenyl substituted with R²¹ groups and at least one R²¹ groupselected from the group consisting of: —SF₅, —OSF₅ and —Si(CH₃)₃; andthe R⁹—R¹⁰— moiety is selected from the group consisting of:


57. The compound of claim 56 wherein R⁷ is selected from the groupconsisting of:


58. The compound of claim 45 selected from the group consisting of:compounds 9, and 15 to
 26. 59. A pharmaceutical composition comprising atherapeutically effective amount of a compound of claim 45 or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable carrier.
 60. A method of modulating gamma-secretasecomprising administering an effective amount of one or more compounds ofclaim 45 or a pharmaceutically acceptable salt thereof to a patient inneed of such treatment.
 61. A method of inhibiting the deposition ofamyloid protein in, on or around neurological tissue, comprisingadministering an effective amount of one or more compounds of claim 45or a pharmaceutically acceptable salt thereof to a patient in need oftreatment.